日本組織適合性学会誌第21巻1号

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1 HLA 5 QCWS 6 25 HLA 7 QCWS HLA-QC 11 DNA Luminex 15 DNA SSO INNO-LiPA 17 DNA SSP 19 DNA SBT 20 DNA HLA 23 FlowPRA 25 LABScreen 27 WAK&ICFA DNA-QC QCWS 35 総説 HLA MHC Major Histocompatibility Complex Official Journal of Japanese Society for Histocompatibility and Immunogenetics JSHI

2 Major Histocompatibility Complex 2014; 21 (1): 1 第 23 回日本組織適合性学会大会のご案内 MHC MHC MHC QCWS 13 会期 : 会場 : TEL 大会内容 ( 予定 ) 1 James McCluskey FAA Professor Microbiology and Immunology, Deputy Vice Chancellor Research, The University of Melbourne, Australia Kyung-Suk Suh Professor Department of Surgery, Seoul National University College of Medicine, Seoul, Korea QC QCWS 5 大会事務局 [email protected]

3 Major Histocompatibility Complex 2014; 21 (1): 年度学会賞ならびに学術奨励賞の募集について会員の皆様助成内容応募資格

4 2014 MHC 2014; 21 (1) 7 MHC 応募推薦方法 [email protected] 1 A4 1 FAX 2 A A [email protected] FAX 選考および結果通知について

5 MHC 2014; 21 (1) 受賞者にかかる義務について助成金の使途 7. 問い合わせ先 Tel: Fax: jshijimu@ kumamoto-u.ac.jp [email protected] [email protected] 4

6 Major Histocompatibility Complex 2014; 21 (1): 5 組織適合性検査技術者認定制度平成 26 年度認定 HLA 検査技術者講習会のお知らせ日時 : 会場 : 23 テキスト : 1 受講証明書 : 1 1 内容 : 35 (1)HLA に関する基礎医学的な講演 HLA (2)HLA タイピングあるいは抗 HLA 抗体検査に関する講演 HLA 16th IHWS 39th ASHI HLA (3) 臓器移植の臨床医学に関する講演 HLA 5

7 Major Histocompatibility Complex 2014; 21 (1): 6 QCWS ミニ集会の開催および参加希望者募集の案内について QCWS QCWS QCWS QCWS 1 QCWS HLA HLA QCWS 1 HLA QCWS 1 HLA QCWS 2 HLA QCWS

8 Major Histocompatibility Complex 2014; 21 (1): 7 9 平成 25 年度認定 HLA 検査技術者講習会アンケート集計結果 :00 12:00 22 A B 4F % % 1 1.3% % % % % 6 7.9% 2 2.6% % % 8 9.9% 5 6.1% 2 2.5% 1 1.2% 8 9.9% 3 3.7% % % 3 4.2% % 1 2.2% 7

9 MHC 2014; 21 (1) 25 HLA % % HLA 4.0 HLA

10 25 HLA MHC 2014; 21 (1) % 2 11% 9 9

11 Major Histocompatibility Complex 2014; 21 (1): 10 日本組織適合性学会認定制度委員会 QCWS 部会名簿 (2014 年 ) DNA-QC -QC 10

12 Major Histocompatibility Complex 2014; 21 (1): 第 17 回 HLA-QC ワークショップレポート 17 HLA-QC 1) 1) QCWS # 1) 1. ワークショップの経過 25 1 QCWS HP DNA-QC 67 QC 50 1 DNA-QC QC 21 QCWS QCWS DNA-QC 53 QC QCWS MHC 2.QCWS のテーマおよび試料選択について DNA-QC DNA 2 DNA DNA HLA ambiguity 5 QCWS HLA HLA 4 DNA QC 3 4 # QCWS 1) 1) 2) 3) 4) 5) 6) 2) 7) 8) 9) 10) 11) 12) 13) 14) 1) 2) 3) 4) 5) 6) 7) 8) 9) 10) 11) 12) 13) 14) 11

13 MHC 2014; 21 (1) HLA HLA-C IgM HLA 2 QC QC DNA-QC 3. 解析方法 DNA-QC Luminex SSO SSO SSP SBT QC FlowPRA 17 HLA-QC Lab Screen WAK Flow ICFA 4 HLA-QC 1) タイピング結果解析 Luminex SSO SSO SSP SBT 表 1 17 QCWS 12

14 17 HLA-QC MHC 2014; 21 (1) HLA 2 FlowPRA Lab Screen HLA WAK Flow ICFA 3 DNA 5.QCWS サンプルの総合結果 DNA DNA 1 DNA Ambiguity HLA- A B C DR IMGT/HLA HLA- DQB1 DPB HLA HLA 0.1% 0.1% 表 2 17 HLA-QC DNA 13

15 MHC 2014; 21 (1) 17 HLA-QC 表 3 17 HLA-QC 14

16 第 17 回 HLA-QC ワークショップレポート 17 HLA-QC DNA Luminex 1) 1) 1. 概要 Luminex DNA-QC % 7 OneLambda LABType 12 LABType HD 10 WAKFlow 20 5 LABType 12 6 HLA-DP DQ HLA-A, B, C, DR LABType HD WAKFlow HLA-A, B HLA-C % HLA-DRB % HLA-DRB3/4/ % HLA-DQA % HLA- DQB % HLA-DPA % HLA-DPB % 2. 解析方法 HLA-A, B, C, DRB %CV Pmin/Nmax P/N 3 17 QC 3. 結果と考察 1 ambiguity 2 CSV 4 H2501 H2504 HLA-C Exon3 %CV 54.6% %CV 40% 4 Pmin/Nmax False Negative False Positive QCWS CD-ROM 15

17 MHC 2014; 21 (1) 3 HLA 2 3 False Positive False Negative False Positive 17 HLA-QC 4. まとめ HLA QCWS 16

18 第 17 回 HLA-QC ワークショップレポート 17 HLA-QC DNA SSO INNO-LiPA 1) 1) 1. はじめに INNO-LiPA Dynal RELI SSO INNO-LiPA QCWS 解析結果 7 1 SSP HLA-C DQ 1 HLA-DR DRB3/4/5 decoder 1 1) 結果判定 I 2 ambiguity H2504 ambiguity 6 ambiguity 4 ambiguity II decoder ambiguity 1 ambiguity 1 false positive 2)Ambiguity の違いについて ambiguity ambiguity ambiguity ambiguity 3) 反応状態について 4 PCR False negative 25D26 False positive 1 3. おわりに HLA 17

19 MHC 2014; 21 (1) HLA HLA 17 HLA-QC Ambiguity 18

20 第 17 回 HLA-QC ワークショップレポート 17 HLA-QC DNA SSP 1) 1) 1. 概要 1) 参加状況 SSP 31 46% 4 SSP ) 参加部門 SSP SSP 3) 使用試薬 low resolution 5 medium resolution 2 medium resolution Micro SSP OneLambda Micro SSP JPN 22 SSP 71% 2. 解析結果および考察 QCWS Consensus Allele 1 2 SSP 3 false positive false negative 1) 判定ミス (miss assign) false positive ambiguity ambiguity 2) 相対的反応データの不備 8 false positive まとめ false positive SSP SSP 1 19

21 第 17 回 HLA-QC ワークショップレポート 17 HLA-QC DNA SBT 1) 1) 1. はじめに (HP 掲載結果 : 図 1) 7 SBT 6 SS- SBT 2 SBT AlleleSEQR HLA typing kits CELERA 6 1 SeCore Sequencing Kits invitrogen SBT RESOLVER CONEXIO Assign SS-SBT 2 1 GS Junior GS Junior Titanium sequencing Kit Roche 1 Ion PGM Ion PGM 200 Sequencing Kit Lifetechnologies Omixon Target Automated NGS data processing system Suzuki Assign MPS 2. 使用キットについて QCWS 3 AlleleSEQR HLA typing kits CELERA SeCore Sequencing Kits invitrogen SBT RESOLVER CONEXIO HLA-A B C DRB1 DQB1 DPB1 2 HLA AlleleSEQR SeCore DPB1 Locus Sequencing Kits SBT RESOLVER kits HLA-C 1 7 AlleleSEQR typing kits SeCore DPB1 Locus Sequencing Kits 3. 結果及び考察 1)SBT 法での解析結果と考察 AlleleSEQR HLA typing kits CELERA Assign QCWS IMGT/HLA Assign HLA-DRB1 3 2 Forward 2 Reverse Codon86 Codon86 HLA-DRB1 86 GTG Assign Codon86 GTG QCWS H2503 Codon86 HLA- DRB1*01:01/50 DRB1*04:03:01 SBT high resolution

22 17 HLA-QC MHC 2014; 21 (1) 6 H2503 HLA-C 1 7 HLA II.I 2 C*05:01/08:02/+ C*07:02/17/37/+ H2503 H2504 HLA-DPB1 1 H2503 HLA-DPB1*04:02/105:01,- H2504 HLA- DPB1*05:01/135:01,- 8 SeCore DPB1 Locus Sequencing Kits H2504 HLA-DRB1 DR14 DR14 Codon86 GTG 9 1 DR14 HLA-DRB1*14:01 DRB1*14:06 2)SS-SBT 法での解析結果と考察 QCWS SS-SBT 2 SS-SBT 5ʹUTR 3ʹUTR DRB3/4/5 2 GS Junior Roche QCWS IMGT/HLA Omixon Target Automated NGS data processing system Suzuki Assign MPS SS-SBT high resolution / SS-SBT QCWS SS-SBT 1 H2504 HLA-B 1 13 undefined H2504 HLA-DRB1 DRB1*14:54 13 SBT DRB1*14:01 DRB1*14:06 SS-SBT HLA-DRB1 DRB1*14:06 PCR SS-SBT DRB1 DRB1*14:06 PCR SS-SBT 2 H2503 HLA-C HLA 14 H2503 SBT HLA-B B*07:02:01 HLA-B*44:02:01:01 HLA-C C*05:01:01:02 C*07*02:01:03 HLA-C*05:03 SS-SBT 2 1 GS Junior Roche GS Junior Titanium sequencing kit 1 Ion PGM Lifetechnologies Ion PGM 200 bp sequencing kit GS Junior 500 bp Ion PGM 200 bp Kit 150 bp H2503 HLA-B HLA-C 15 SS-SBT H2503 HLA 21

23 MHC 2014; 21 (1) PCR 1 B*44:02:01:01 C*05: bp GS Junior 500 bp HLA-C*05:03 Ion PGM 150 bp C*05:03 4. まとめ SBT SBT 17 HLA-QC SS-SBT SS-SBT QC 22

24 第 17 回 HLA-QC ワークショップレポート 17 HLA-QC DNA HLA 1) 1) 1. 概要 17 QCWS 66 A B C DRB1 DRB3/4/5 DQB1 DPB1 DQA1 DPA1 HLA-A B % DRB % C % HLA 表記法の改訂と注意点 HLA 改訂箇所 (1) HLA 2010 II ambiguity / 2 / 3 4 /+ Resolution Low Resolution 4 High Resolution 2-2. 改訂箇所 (2) IV HLA HLA DNA HLA HLA HLA / H2501 A*24:02/03/04/+ HLA A24/2403 A*24:02/11/20/+ HLA A24 A*24:02 HLA A24 HLA HLA HLA 2 HLA HLA 1 HLA 2-3. 改訂箇所 (3) IV HLA HLA-C HLA WHO HLA HLA 1 23

25 MHC 2014; 21 (1) 表 1 HLA HLA HLA HLA A*02:03 A203 A*02:10 A210 A*24:03 A2403 A*24:10 A2403 A*24:23 A2403 A*24:33 A2403 B*39:01 B3901 B*39:02 B3902 B*51:02 B5102 B*51:03 B5103 DRB1*01:03 DR103 DRB1*14:03 DR1403 DRB1*14:04 DR1404 HLA HLA-C HLA- C*12 C*18 HLA 1 HLA HLA HLA-C HLA-C*12 C*18 HLA 1 HLA H2501 C*14:02 HLA Cw14 H2502 C*12:02 HLA Cw12 3. 減点対象例 17 HLA-QC 考察表 2 L 15 A*24:02/02L/03/+ N 15 A*24:02/09N/10/+ : 5 A* A*24 02/03/04/+ * 5 A24:02/03/04/+ 5 A*24:02/03/04/+ 5 *24:02/03/04/+ 表 3 HLA 10 A203/2 B62/B15 HLA Cw12 blank 0 10 Cw07 Cw W 10 CW1 Cw w 10 C7 HLA HLA QCWS 24

26 第 17 回 HLA-QC ワークショップレポート 17 HLA-QC FlowPRA 1) 1) 1. 概要 17 HLA-QCWS FlowPRA HLA 22 FlowPRA Screening test HLA Class I 22 HLA Class II FlowPRA Single Antigen test HLA Class I 4 HLA Class II 3 Becton, Dickinson and Company10 Beckman Coulter12 2. 解析方法 FCS FlowJo Tree Star, Inc. USA FlowPRASingle Antigen test FlowPRA 3.FlowPRA Screening test 解析結果 4 QCWS HLA Class I HLA Class II SH2501 SH2502 SH2504 SH2503 Sample HLA Class I 100% HLA Class II 100% % HLA Class I II % Nagative control Anti-Human IgG-FITC count Nagative control Anti-Human IgG-FITC SH2502 Sample Control Beads 6 Control Beads Adsorb- Out Sample Anti-Human IgG-FITC 4.FlowPRASingle Antigen test 解析結果 Negative Control Serum 4 2 Negative Control 25

27 MHC 2014; 21 (1) Serum 1 Donor Serum 1 Negative Control SH2502 QC Sample FlowPRA Screening test Control Beads Adsorb-Out FlowPRA Screening test 17 HLA-QC 5. まとめ FlowPRA Screening test % FlowPRA Single Antigen test Negative Control Serum 26

28 第 17 回 HLA-QC ワークショップレポート 17 HLA-QC LABScreen 1) 1) HLA 1. はじめに LABScreen LABScreen Mixed 1 LABScreen Mixed Multi PRA LabScreen Single Antigen SA 10 SA 19 Mixed 6 PRA 5 Multi 1 1 HLA Fusion 2. 結果の解析および考察 1) 判定の不一致 Class I Class II SH2403 SH2403 Class II 23 3 Cutoff MFI 2)cut off の設定について HLA Fusion cut off MFI1,000 cutoff 2, ) 実測値のバラツキ Positive Control Beads MFI 10,000 beads 3,000 QCWS 4) その他の判定不一致 1 1 MFI 3. まとめ LABScreen HLA / cutoff cutoff SA SA PRA HLA 27

29 第 17 回 HLA-QC ワークショップレポート 17 HLA-QC WAK&ICFA 1) 1) 1. はじめに WAKFlow HLA WAKFlowMR I 13 3 II 8 2 Fig. 1 I 3 N0A M0B 7 6 II 1 L0A 7 M0A 2 Table 1 17 QC HLA WAKFlow 2.WAKFlow-MR クラス I BB PB Fig SH2503 SH BB PB 2 Fig. 3 Fig. 6 Index Fig. 3 Fig. 6 1) 判定結果について Table 2 Table 3 6 Index Table 7 10 LAB- Screen Single Antigen LS-SA BNV 10,000 5,000 10,000 2,000 5,000 Table 3 6 Index Table 7 10 Table ) 判定不一致例について Fig S28 S Table Index LS-SA BNV 28

30 17 HLA-QC MHC 2014; 21 (1) 3) 判定方法の再確認 Table 15 WAKFlow )HLA-C- ローカスに対する抗体検出の注意点 WAKFlow class I HLA-C HLA-A B Table 16 HLA-C SH2503 LS-SA HLA-Cw6 7 BNV 15,000 HLA-Cw4 8,000 WAKFlow MR class I 2 HLA-C 3.WAKFlow-MR クラス II II I Table 17 BB PB Lot. L0A 46 BB Fig. 8 Index Index Fig Table まとめ 29

31 第 17 回 HLA-QC ワークショップレポート 17 HLA-QC 1) 1) 1. その他検査法 LABScreen Flow- PRA LCT AHG-LCT 3 ICFA 2 MPHA 4 3 LCT AHG-LCT C1qScreen ICFA LABScreen MPHA 2. クロスマッチ SH2501 LCT AHG-LCT 6 FCM 7 ICFA 11 3 LCT AHG-LCT FCM GeoMean SN ICFA LABScreen SH DNA H2503 H2504 SH2501 H2503 SH2501 H2504 DNA QC 17 30

32 第 17 回 HLA-QC ワークショップレポート 17 HLA-QC DNA-QC 1) 1) 1. はじめに DNA-QC HLA HLA DNA 17 QC DNA 2. 使用タイピング法について SSP SSO INNO-LIPA Luminex SBT SS-SBT SSP 56.1% SSO Luminex SSO INNO-LIPA 100% HLA HLA-A, B 100% SSP SSO INNO-LIPA HLA-A, B, DRB1 100% SBT HLA-A, B, C, DRB1 100% 3. 結果評価 3.1 概要 HLA-QC HLA HLA 3 HLA-A, B, C, DRB1 3.2 判定結果の評価 % 10% SBT 結果表記の評価 % 16th QCWS 94.3% 17th QCWS 94.1% 5% 試験検査状況の評価 HLA A, B, C 31

33 MHC 2014; 21 (1) Luminex GenoSearch SBT A 6 20% B SBT A C B 17 HLA-QC 4. 総合評価 A B 0 60 C A 34 50% B 32 C QCWS 13 32

34 第 17 回 HLA-QC ワークショップレポート 17 HLA-QC 1) 1) 1. 部門別解析 1.1 概要 QC th % 部門別解析 16th IgM 83.0% 100% SH2503 II 100% 100% SH2503 II Consensus LABScreen single antigen 100 Class I 100% 74.0% Class II 96.6% 95.2% 92.6% 2. 結果評価 2.1 抗体 QC 結果評価について 0.67 HP 2.2. 評価結果 1 A % B C % C 2 II SH % 2 LABScreen single antigen 2 37 A % B % C % A B C 33

35 MHC 2014; 21 (1) 3 A 100% B C 95 97% C C II DR DQ 4 Consensus Result Consensus Result 1 8 Consensus Result % High resolution LABScreen Flow PRA single antigen WAKFlow LABScreen QCWS WAKFlow 70% C 17 HLA-QC 1 A B C Flow PRA single antigen C 3. 結語 17th QCWS 16th QCWS 18th QCWS 1) 結果記入シート記載および提出についての注意事項 2) 継続的参加の重要性 QCWS 26.5% Consensus QCWS 34

36 第 17 回 HLA-QC ワークショップレポート 17 HLA-QC QCWS 1) 1) 1. 概要経過 17 QCWS QCWS 4 2 ACD-A 7 ml T ACD-A QCWS 3. 検査方法および試料選択について QCWS #2502 #2504 #2502 CDC CDC 27 AHG-CDC 7 FCXM 25 ICFA 検査結果 90% 5. まとめ 35

38 Major Histocompatibility Complex 2014; 21 (1): 総説 HLA 1) 1) 2) 2) 1) 1) 2) HLA 30,000 1, HLA キーワード : はじめに HLA Mb HLA 1) IMGT/HLA HLA 8,000 2) HLA 3) 30, i ii iii HLA 日本人集団の混合的起源を支持する遺伝学的知見 TEL: [email protected] 37

39 MHC 2014; 21 (1) 4) 5) Y D D-P37.1 6) O-M122 OP-31 D-P37.1 U O-M122 O-P31 U 1 D-P37.1 図 1 Y Y Hammer 6) 1 5 HLA O-M122 O-P31 O-M122 O-P31 DNA M12 Y D 7) DNA SNP 8) HLA 8,9) HLA 遺伝子多型から見た日本人集団の祖先の推測 HLA 10) HLA 5) 11,12) A*24-B*54-DRB1*04:05 11) 13) 11) HLA 10) HLA 14 16) 38

40 HLA MHC 2014; 21 (1) 図 2 HLA D 17 HLA 日本人集団の祖先集団を推測する HLA 領域の遺伝的痕跡 10 2,000 HLA HLA-A B C DRB1 DPB1 17) principal component score PCS HLA HLA PCS 10 HLA PCS HLA i 2 CL3 CL4 ii 39

41 MHC 2014; 21 (1) 2 CL1 2 CL2 HLA A*24:02-C*01:02-B*54:01-DRB1*04:05-DPB1*05:01 i ii i A*24:02-C*12:02-B*52:01-DRB1*15:02-DPB1*09:01 A*33:03-C*14:03-B*44:03-DRB1*13:02-DPB1*04:01 CL1 A*02:06 B*35:01 A*33:03-C*14:03-B*44:03-DRB1*13:02- DPB1*04:01 DPB1*04:01 18) 10 3A PCS HLA A*24:02 C*03:04 C*07:02 B*40:02 DRB1*09:01 3B A*24:02-C*03:04-B*40:02 A24-Cw10-B61 4 HLA 17) SNP 19) pincer model 20,21) HLA pincer model 22) ) 24) first American 25) HLA A*24:02-C*03:04-B*40:02 first American 17) A*24:02-C*03:04-B*40:02 HLA A*24:02-C*12:02-B*52:01-DRB1*15:02-DPB1*09:01 A*33:03-C*14:03-B*44:03-DRB1*13:02-DPB1*04:01 A*24:02-C*01:02-B*54:01-DRB1*04:05- DPB1*05:01 40

42 HLA MHC 2014; 21 (1) 図 3 HLA A PCS B 17 図 4 HLA A*24:02-C*03:04-B*40:02 A24-Cw10-B61 41

43 MHC 2014; 21 (1) さいごに HLA 4 I 2 3 II 2 HLA 26 28) HLA 謝辞 HLA PGx JPDSC JPDSC DNA 引用文献 1) Shiina T, Hosomichi K, Inoko H, et al.: The HLA genomic loci map: Expression, interaction, diversity and disease. Journal of Human Genetics (54): 15 39, ) Robinson J, Waller MJ, Parham P, et al.: IMGT/HLA and IMGT/ MHC: Sequence databases for the study of the major histocompatibility complex. Nucleic Acids Research (31): , ) Vina MA, Hollenbach JA, Lyke KE, et al.: Tracking human migrations by the analysis of the distribution of HLA alleles, lineages and haplotypes in closed and open populations. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences (367): , ) Hanihara K: Dual structure model for the population history of the Japanese. Japan Review (2):1 33, ) Omoto K, Saitou N: Genetic origins of the Japanese: A partial support for the dual structure hypothesis. American Journal of Physical Anthropology (102): , ) Hammer MF, Karafet TM, Park H, et al.: Dual origins of the Japanese: Common ground for hunter-gatherer and farmer Y chromosomes. Journal of Human Genetics (51): 47 58, ) Tanaka M, Cabrera VM, Gonzalez AM, et al.: Mitochondrial genome variation in eastern Asia and the peopling of Japan. Genome Research (14): , ) Yamaguchi-Kabata Y, Nakazono K, Takahashi A, et al.: Japanese HLA population structure, based on SNP genotypes from 7003 individuals compared to other ethnic groups: Effects on populationbased association studies. American Journal of Human Genetics (83): , ) Yamaguchi-Kabata Y, Tsunoda T, Kumasaka N, et al.: Genetic differences in the two main groups of the Japanese population based on autosomal SNPs and haplotypes. Journal of Human Genetics (57): , ) Tokunaga K, Imanishi T, Takahashi K, et al.: On the origin and dispersal of East Asian populations as viewed from HLA haplotypes. In Akazawa T, Szathmary EJE (Eds.), Prehistoric Mongoloid Dispersals, Oxford University Press, Oxford ) Hatta Y, Ohashi J, Imanishi T, et al.: HLA genes and haplotypes in Ryukyuans suggest recent gene flow to the Okinawa islands. Human Biology (71): , ) Bannai M, Ohashi J, Harihara S, et al.: Analysis of HLA genes and haplotypes in Ainu (from hokkaido, northern Japan) supports the premise that they descent from upper paleolithic populations of East Asia. Tissue Antigens (55): , ) Tajima A, Hayami M, Tokunaga K, et al.: Genetic origins of the Ainu inferred from combined DNA analyses of maternal and paternal lineages. Journal of Human Genetics (49): , ) Tokunaga K, Ishikawa Y, Ogawa A, et al.: Sequence-based association analysis of HLA class I and II alleles in Japanese supports conservation of common haplotypes. Immunogenetics (46): , ) Saito S, Ota S, Yamada E, et al.: Allele frequencies and haplotypic associations defined by allelic DNA typing at HLA class I and class II loci in the Japanese population. Tissue Antigens (56): , ) Lee KW, Oh DH, Lee C, et al.: Allelic and haplotypic diversity of HLA-A, -B, -C, -DRB1, and -DQB1 genes in the Korean population. Tissue Antigens (65): , ) Nakaoka H, Mitsunaga S, Hosomichi K, et al.: Detection of ancestry informative HLA alleles confirms the admixed origins of Japanese population. PLoS One (8): e60793, ) Kawashima M, Ohashi J, Nishida N, et al.: Evolutionary analysis of classical HLA class I and II genes suggests that recent positive selection acted on DPB1*04:01 in Japanese population. PLoS One (7): e46806, ) HUGO Pan-Asian SNP Consortium, Abdulla MA, Ahmed I, et al.: Mapping human genetic diversity in Asia. Science (326): , ) Cavalli-Sforza LL, Menozzi P, Piazza A: The history and geography of human genes. Princeton University Press, Princeton ) Karafet T, Xu L, Du R, et al.: Paternal population history of East Asia: Sources, patterns, and microevolutionary processes. American Journal of Human Genetics (69): ,

44 HLA MHC 2014; 21 (1) 22) Di D, Sanchez-Mazas A: Challenging views on the peopling history of East Asia: The story according to HLA markers. American Journal of Physical Anthropology (145): 81 96, ) Goebel T, Waters MR, O Rourke DH.: The late pleistocene dispersal of modern humans in the Americas. Science (319): , ) Rasmussen M, Li Y, Lindgreen S, et al.: Ancient human genome sequence of an extinct Palaeo-Eskimo. Nature (463): , ) Reich D, Patterson N, Campbell D, et al.: Reconstructing native American population history. Nature (488): , ) Hosomichi K, Jinam TA, Mitsunaga S, et al.: Phase-defined complete sequencing of the HLA genes by next-generation sequencing. BMC Genomics (14): 355, ) Wang C, Krishnakumar S, Wilhelmy J, et al.: High-throughput, high-fidelity HLA genotyping with deep sequencing. Proceedings of the National Academy of Sciences of the United States of America (109): , ) Shiina T, Suzuki S, Ozaki Y, et al.: Super high resolution for single molecule-sequence-based typing of classical HLA loci at the 8-digit level using next generation sequencers. Tissue Antigens. (80): ,

45 MHC 2014; 21 (1) HLA The Admixed Origin of Japanese Population from HLA Alleles Hirofumi Nakaoka 1), Kazuyoshi Hosomichi 1), Shigeki Mitsunaga 2), Hidetoshi Inoko 2), Ituro Inoue 1) 1) Division of Human Genetics, Department of Integrated Genetics, National Institute of Genetics 2) Division of Molecular Life Science, School of Medicine, Tokai University The polymorphisms in the human leukocyte antigen (HLA) region are powerful tool for studying human evolutionary processes such as migration, admixture, natural selection and genetic adaptation. The origin of modern Japanese has long been debated. It is thought that there are at least two waves of migrations to the Japanese Archipelago. The ancestors of the Jomon people migrated to the Japanese Archipelago in the Upper Paleolithic age (approximately 30,000 years ago). The new migrants, the Yayoi people, came through the Korean Peninsula in the Aeneolithic period (1,000 BC to 300 AD). The prevailing model for peopling of Japan is the admixture model or dual structure model in which modern Japanese was formed by admixture between the Jomon and Yayoi people. We briefly review findings that support the admixture model for peopling of Japanese Archipelago, and introduce recent studies for exploring genetic footprints of the migration route of prehistoric ancient populations. Key Words: Japanese population, human leukocyte antigen, admixture, migration, evolution

46 Major Histocompatibility Complex 2014; 21 (1): 抄録集 TEL: ips TEL: [email protected] 45

47 MHC 2014; 21 (1) 12 参加費 1 2, , ,000 会議等 :50 14: :30 13: :00 会場地図大阪府赤十字血液センター 7 階会議室 TEL JR 350 m 46

48 12 MHC 2014; 21 (1) プログラム受付開始午前の部オープニングセミナー 1 2 HLA-F I 一般演題 (1) 1 NAIT HPA-15b 2 HLA-DPB1 1) 1) 2) 1) 2) 3 FlowPRA Screening HLA 1) 1) 1) 1) 2) 3) 3) 1) 2) 3) 4 WAKFlowHLA I HR 5 Single Antigen PRA 1) 1) 1) 1) 1) 1) 1) 1) 1) 1) 2) 1) 1) HLA 1) NPO 2) 47

49 MHC 2014; 21 (1) 12 一般演題 (2) HLA 6 ips NGS 4 HLA 1) 1) 2) 2) 2) 2) 2) 1) 3) HLA 1) 2) ips 3) 7 Miseq HLA 1) 1) Wyatt Nelson 2)3) 3)4) 1) 1) 1) 1) 1) 1) 1) Daniel E. Geraghty 2)3) 1) HLA 1) Fred Hutchinson Cancer Research Center 2) Scisco Genetics, Inc. 3) 4) 8 A, B, DR, DQ, DP 1) 1) 1) 1) 1) 1) 1) 1) 1) 1) 2) 1) 1) HLA 1) NPO 2) 9 HLA-8/8 HLA-DPB1 disparity 1) 1) 2) 3) 1) 2) 3) 昼食世話人会総会 48

50 12 MHC 2014; 21 (1) 午後の部ブリーフセッション ips ASHI American Society for Histocompatibility and Immunogenetics 39th Annual Meeting HLA シンポジウム ips ips 1 ips ips 2 ips ips 3 ips ips 特別講演 HLA 17 懇親会 49

51 MHC 2014; 21 (1) 12 10:00 11:00 オープニングセミナー 1 2 HLA-F I 50

52 12 MHC 2014; 21 (1) 1 ISBT Landsteiner ABO 20 DAT 1990 ISBT Blood Group Allele Terminology BLOODChip TM IDCORE XT GRIFOLS BioArray TM IMMUCOR ABO ABO TM MBL 51

53 MHC 2014; 21 (1) 12 2 HLA-F I HLA-F Geraghty HLA class I HLA-E, -F, -G HLA class I HLA-E -G HLA-F HLA-F HLA-F 1) B, T, NK, monocyte Treg 2)3) extravillous trophoblast HLA-F 4)5) HLA-F HLA-F HLA class I HLA-I cross-presentation 6)7) HLA-I CD8 T HLA class II HLA-II HLA-I T HLA-I crosspresentation 8) cross-presentation HLA-I b2m open conformer HLA homodimer cis interaction 9) HLA-F b2m open conformer HLA-I open conformer HLA-I open conformer 50 HLA-F HLA-F HLA-I lysosome HLA-I Golgi HLA-I b2m T HLA-F HLA-I open conformer HLA-F HLA-I 2 open conformer heterodimer NK Killer Ig-like receptor KIR 10) HLA-F HLA-I open conformer KIR 1) Lee N, Ishitani A, and Geraghty DE. (2010). HLA-F is a surface marker on activated lymphocytes. Eur J Immunol 40: ) Zhang X, Lin A, Zhang JG, Bao WG, Xu DP, Ruan YY, Yan WH. (2013) Alteration of HLA-F and HLA I antigen expression in the tumor is associated with survival in patients with esophageal squamous cell carcinoma. Int J Cancer 132(1): ) Sageshima N, Ishitani A, et al. HLA-F expression on tumor tissue. in submittion. 4) Ishitani A, Sageshima N, Lee N, Dorofeeva N, Hatake K, Marquardt H, Geraghty, DE. (2003) Protein expression and peptide binding suggest unique and interacting functional roles for HLA-E, F, and G in maternal-placental immune recognition. 52

54 12 MHC 2014; 21 (1) J Immunol 171: ) Shobu T, Sageshima N, Tokui H, Omura M, Saito K, Nagatsuka Y, Nakanishi M, Hayashi Y, Hatake K, Ishitani A. (2006) The surface expression of HLA-F on decidual trophoblasts increases from mid to term gestation. J Reprod Immunol 72(1 2): ) Goodridge JP, Burian A, Lee N, Geraghty DE. (2010). HLA-F complex without peptide binds to MHC class I protein in the open conformer form. J Immunol 184: ) Goodridge JP, Lee N, Burian A, Pyo CW, Tykodi SS, Warren EH, Yee C, Riddell SR, Geraghty, DE. (2013) HLA-F and MHC-I open conformers cooperate in an MHC-I antigen cross presentation pathway. J Immunol 191: ) Joffre OP, Segura E, Savina A, Amigorena S. (2012) Crosspresentation by dendritic cells. Nat Rev Immunol 12: ) Arosa FA, Santos SG, Powis SJ. (2007) Open conformers: the hidden face of MHC-1 molecules. Trends in Immunol 28: ) Goodridge, JP, Burian A, Lee N, Geraghty DE. (2013) HLA-F and MHC-I open conformers are ligands for natural killer cell receptors. J Immunol 191(7):

55 MHC 2014; 21 (1) 12 11:00 11:50 一般演題 (1) 座長 : 荒木延夫 ( 兵庫県赤十字血液センター ) 演題番号 1)~ 5) 54

56 12 MHC 2014; 21 (1) 1 NAIT HPA-15b 1 NAIT neonatal alloimmune thrombocytopenia MPHA NAIT 55: , family 3 NAIT HPA-15b 2 HPA-15 1 HPA-15b 11,000/ μl HLA LABScreen IP-MPHA intact platelet-mpha Fig. 1 HPA-15b EP-MPHA extracted platelet antigen solution- MPHA EP-MPHA n=8 MACE modified antigen capture ELISA GTI PAKPLUS 18 IP-MPHA population study Table 1 family HLA HPA Fig. 2 HPA-15 GPI CD109 CD109 EP EP CD109 calpain EP HPA MPHA Beckman Coulter HPA-15 GTI HPA MACE Luminex CD109 IP-MPHA HPA-15 HLA HLA HPA-15 HPA-15 HLA I CD11b CD109 CD109 Berry HLA-DRB1*13 HLA-DRB1* HLA-DRB1*13 55

57 MHC 2014; 21 (1) 12 56

58 12 MHC 2014; 21 (1) 2 HLA-DPB1 1) 1) 2) 1) 2) HLA HLA-A, B, DR HLA-DP HLA HLA-A, B, DR HLA-DP HLA-DP 2 HLA 1 41 MDS-u HLA A*24:02, - B*27:05, 59:01 DRB1*12:01, 14:02 HLA HLA-B, DRB1, DPB /kg CD / kg 2 61 MDS/MPD HLA A*24:02, - B*15:01, 44:03 DRB1*13:02, 14:06 HLA /kg CD /kg 8/8 1 day29 2 day21 1 DSA HLA 3 random PC 2 1 DSA DP CD34 DP 1 2 HLA HLA-DP DSA CB HLA-DP HLA HLA HLA-DP DP DP DSA 57

59 MHC 2014; 21 (1) 12 3 FlowPRA Screening HLA 1) 1) 1) 1) 2) 3) 3) 1) 2) 3) HLA LABScreen Single Antigen HLA LABScreen Single Antigen FlowPRA Screening FlowPRA Screening Class I 65.1% Class II 48.9% FlowPRA Screening Class I II DTT FlowPRA Screening rpm 20 DTT 56 C 30 DTT 0.005M DTT 37 C 30 Class I 61.9% Class II 51.8% DTT Class I 63.3% Class II 33.3% Class I II DTT Class I II FlowPRA Screening LABScreen Single Antigen FlowPRA Screening LABScreen Single Antigen FlowPRA Screening 58

60 12 MHC 2014; 21 (1) 4 WAKFlowHLA I HR HLA LABScreen Single Antigen LSSA WAKFlowHLA I HR HR HR HLA IgM HLA A24/33 B44/52 Cw12/14 A24/26 B52/62 Cw9/12 A26/33 B44/62 Cw9/14 LSSA A26 149T +144Q 90D GSHTIQR 2 B62 46A 76-80ESLRN =Bw LSSA HR Calmed Score LSSA ESLRN =Bw6 Bw6 Calmed 1,000 5,000 Score6 B*54:01 Calmed Score4: 500 1,000 1 HR Threshold Score6 Score4 HLA HR 59

61 MHC 2014; 21 (1) 12 60

62 12 MHC 2014; 21 (1) 5 Single Antigen PRA 1) 1) 1) 1) 1) 1) 1) 1) 1) 1) 2) 1) 1) HLA 1) NPO 2) HLA LABScreen Single Antigen beads Single HLA LABScreen PRA beads PRA HLA Single PRA HLA Single PRA PRA beads PRA Single Luminex PRA Single Class I 217 Class II 150 EDTA 0.05M allele Single Class I 86 Single Class II 80 beads Single MFI 1,000 beads allele PRA MFI<500 5 allele Class I C*17: % B*45: % A*68:02 9.7% B*15:16 8.8% B*44:02 8.8% Class II DQB1*03: % DQB1*03: % DQB1*03: % DRB3*03: % DRB1*09: % Class I Class II PRA Single HLA HLA non HLA allo 18.9% HLA-A*30:02 1.4% HLA-A*30:02 PRA Single beads HLA HLA HLA-C*17:01 HLA される自然抗体と考えることができる HLA HLA PRA non-allo HLA PRA Single Class I 87% Class II 79% Single PRA cut off 61

63 MHC 2014; 21 (1) 12 62

64 12 MHC 2014; 21 (1) 11:50 12:30 一般演題 (2) HLA 演題番号 6)~ 9) 63

65 MHC 2014; 21 (1) 12 6 ips NGS 4 HLA 1) 1) 2) 2) 2) 2) 2) 1) 3) HLA 1) 2) ips 3) 目的 ips 細胞のドナーバンクにおいては 1 塩基の de novo 変異や挿入欠失を見逃さない細胞樹立前後の同一性確認も必要となるこのためには, 解像度が極めて高い NGS(Next Generation Sequencing) による HLA タイピング技術が有用と考えられる今回は Ion PGM(Life Technologies) を用いて検査を施行したので報告する材料方法 Luminex 法 (A, B, C, DRB1:WAKFlow, DQA1, DQB1, DPA1, DPB1:LABType) にて検査した患者とその両親を 3 家族 1 家族 3 名 (No. 1 3) は Buccal,2 家族 6 名 (No. 4 9) は血液由来を用い, 東海大学で施行されている方法を基に実施した得られた塩基配列の解析については, 各 locus の全 exon 領域における BLAT 解析から類似性の高いアリル候補を IMGT- HLA から選抜し, それをコンピューター上で検証することによりアリル判定を行うスズキ法にてデータ解析を行った結果考察 NGS によるタイピング結果は検体種類に依存することなく, 一部を除いて Luminex 法との整合性が得られた結果を表 1 に示す C 座のタイピング結果が Luminex 法と異なった直接的な原因は,Long PCR 産物の存在を確認したもののアリル判定に用いた有効リード数がほぼ 0 であったことから,Long PCR 後の濃度調製に問題があったと考えられるまた,No.7 の DRB1,DRB3/4/5,DQB1 および DPA1 にて出現が期待されるアリルついても他検体にて問題なく判定されていることから, これも前述と同様の理由と考えられる特に C 座は有効リード数がほぼ 0 にもかかわらず, 片方のアリルのみ homozygote として判定されたことから, 今後,NGS がルーチン化されるにあたってはlocus ごとにdepth,coverage のような NGS 情報に, 多施設とのコンセンサスが得られた, もしくは自施設で妥当性のとれた基準を設ける必要があるそのために現状では自動判定ソフトウェアよりも, それぞれの NGS 情報が確認できるスズキ法が有用であるまた, 日本列島人に珍しいアリルに関しては NGS の方が効率よく判定できると考えるが, 複数回行う PCR の過程がミス判定を引き起こす可能性があるこれを解消する方法として,Luminex 法などの従来法との併用が良策であるが, 今回のように家族検体を用いることも有効な手段であると考えられる最後に,NGS による HLA タイピングは他にも Ambiguity を解消できるという利点があるさらには, コストパフォーマンス, スループット性ともに Luminex 法と大差ないことから, 第 2 区域までの HLA タイピングが Luminex 法に代わる, もしくは第 2 の方法として確立されつつある一方, 第 4 区域までのタイピングは, 決定されている第 4 区域までのアリル配列が乏しいことから, 現時点では未だ難しい技術である東海大学らはこの問題を解決するために, 日本列島人の 99.5% 以上を網羅する第 4 区域までのアリル配列の収集を進めており, 近い将来にプロモーター領域から 3 側非翻訳領域までを網羅する HLA 遺伝子全領域における HLA タイピングの実用化が期待される 64

66 12 MHC 2014; 21 (1) 65

67 MHC 2014; 21 (1) 12 7 MiSeq HLA 1) 1) Wyatt Nelson 2)3) 3)4) 1) 1) 1) 1) 1) 1) 1) Daniel E. Geraghty 2)3) 1) HLA 1) Fred Hutchinson Cancer Research Center 2) Scisco Genetics, Inc. 3) 4) HLA Luminex Sanger NGS Next generation Sequencing Ambiguity MiSeq Illumina HLA Luminex 32 1 negative control Buccal 13 9 UCLA University of California, Los Angels Immunogenetics Center DNA/summaryDNA.htm 8 1 Buccal 2 Luminex HLA-A, B, C, DRB1 WAKFlow HLA-DQA1, DQB1, DPA1, DPB1 LABtype, Onelambda MiSeq HLA-A, B, C, DRB1, DRB3, 4, 5, DQA1, DQB1, DPA1, DPB1 Scisco Genetics exon PCR Barcode, Adaptor MiSeq MiSeq Bridge PCR A, T, C, G CCD IMGT Q Luminex MiSeq HLA MiSeq HLA PB, Buccal Luminex PCR PCR PCR ASHI family4- C Luminex C*08:03/ MiSeq C*08:06 Luminiex 4 MiSeq MiSeq ASHI Luminex MiSeq HLA 66

68 第 12 回日本組織適合性学会近畿地方会 MHC 抄録集 ; 21 (1)

69 MHC 2014; 21 (1) 12 8 A, B, DR, DQ, DP 1) 1) 1) 1) 1) 1) 1) 1) 1) 1) 2) 1) 1) HLA 1) NPO 2) HLA-A, B, DR GVH/HVG C DQ DP DQA1, DPA1 HLA-A, B, DR, DQ, DP DQ DP 394 1,904 Luminex WAKFlow LABType HLA DQA1-DQB1 DPA1-DPB1 HF DQA1, DPA1 HLA-A, B, DR, DQ, DP HF LD RD 1 2 HLA-A, B, DR 5 DQ DP 3 Luminex Ambiguity 4 2 DQA1-DQB1 DPA1-DPB1 HF LD RD 1 DQA1, DPA1 Ambiguity 2 NGS Next Generation Sequencing HLA-A, B, DR, DQ, DP HF HLA-A, B, DR HLA-A, B, DR HLA-DQ, DP DQ, DP HLA-A, B, C, DR DP DQ C 68

70 12 MHC 2014; 21 (1) 69

71 MHC 2014; 21 (1) 12 9 HLA-8/8 HLA-DPB1 disparity 1) 1) 2) 3) 1) 2) 3) 16thIHIW HLA-A B C DRB1 8/8 matched HSCT DQB1 10/10 matched HSCT DPB1 12/12 matched HSCT Fleishhauer Zino permissive P non-permissive NP GvHD nonrelapse mortality HLA-DPB1 T cell epitope TCE T 10/10 matched HSCT HLA-DPBI match M P NP HLA U R 70 HLA HLA-C, DQA1/DQB1, DPA1/DPB1 LABType One Lambda HLA-A, B, C, DRB1, DPB1 WAKFlow TCE3 TCE4 match M permissive P non-permissive NP R HLA-DQA1/DQB1, DPA1/DPB1 8/8 matched HSCT=12/12 matched HSCT U HLA-DQA1/DQB1 8/8 matched HSCT=10/10 matched HSCT DPA1/DPB1-M % DPA1/DPB1-P % DPA1/DPB1-NP TCE % DPA1/DPB1-NP TCE % DPA1/DPB1-M P TRM 1 NRM 9 Re 4 DPA1/ DPB1-NP 8 6 TRM 2 NRM 3 Re 1 M P NP M NP 8/8 matched HSCT NP HLA-DP 70

72 12 MHC 2014; 21 (1) 14:00 14:20 ブリーフセッション ips ASHI(American Society for Histocompatibility and Immunogenetics)39th Annual Meeting に出席して 1) 1) 2) HLA 1) ips 2) 71

73 MHC 2014; 21 (1) 12 ASHI American Society for Histocompatibility and Immunogenetics 39th Annual Meeting 1) 1) 2) HLA 1) ips 2) 39 ASHI Chicago Sheraton Chicago Hotel and Towers Poster Session 188 Keynote address ips cells 1 Plenary lecture NK Tolerance Award Complement 9 Symposium 9 Affiliate Meeting 6 Workshop 28 Abstract Session 46 Hot Topics C1q NGS Next Generation Sequencing HLA KIR killer immunoglobulin like receptors KIR KIR A/B / HLA C1qScreen C1qScreen CDC complement-dependent cytotoxicity CDC NMDP/ CIBMTR ABO EMBT BM 22% PB 72% CB 6% CB PB HLA 10% % Caucasian 40th ASHI Denver Colorad ASHI JSHI JSHI 5 JSHI 72

74 12 MHC 2014; 21 (1) 14:20 15:50 シンポジウム ips ips 1 ips ips 2 ips ips 3 ips ips 73

75 MHC 2014; 21 (1) 12 1 ips ips ES ips ES ips ips ips 90% ips in vitro in vivo Mae S. et al., 2013 ips ips 2 TTNPB, AM580 Araoka T. et al., 2014 ips disease modeling ips ADPKD Alport ips ips ips ips 74

76 12 MHC 2014; 21 (1) 2 ips 1) 1) 1) 1) 2) 2) 2) 3) 4) 1) 1)5)6) ips 1) 2) 3) 4) 5) 6) HLA ips ips ips HLA ips autograft MHC MHC allograft MRI, PET PET allograft IgG 1 PK11195 PET autograft, allograft ips HLA ips HLA MHC ips HLA 75

77 MHC 2014; 21 (1) 12 3 ips ips ips ips 2011 ES 30 ips T ips ips ips 76

78 12 MHC 2014; 21 (1) 16:00 17:00 特別講演造血幹細胞移植と HLA 77

79 MHC 2014; 21 (1) 12 HLA 1970 HLA 1990 HLA 4000 HLA HSCT GVHD GVHD GVL HLA HSCT HLA HSCT HLA GVHD HLA HLA HLA HLA HLA HLA HLA 2 HSCT HLA 1 HLA multi-snps HLA LD HLA 2 HLA HLA-DPB1 3 HLA 4 NK KIR 5 HSCT global 6 78

80 Major Histocompatibility Complex 2014; 21 (1): 日本組織適合性学会誌 MHC の投稿規定 I. 投稿について内容 :MHC 資格 : 倫理 : World Medical Assembly 1980 種類 : 審査 : 著作権 : 掲載料 : 別冊 : II. 原著執筆書式 1. 執筆要項 Microsoft Word Microsoft PowerPoint CD CD A 第 1 頁目 FAX Susceptibility gene for non-obstructive azoospermia in the HLA class II region: correlations with Y chromosome microdeletion and spermatogenesis. Tetsuya Takao 1), Akira Tsujimura 1), Masaharu Sada 2), Reiko Goto 2), Minoru Koga 3), Yasushi Miyagawa 1), Kiyomi Matsumiya 1), Kazuhiko Yamada 2), Shiro Takahara 1) 1) Department of Urology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan 2) Department of Regenerative Medicine, National Cardiovascular Center, Suita, Osaka, Japan 3) Department of Urology, Osaka Central Hospital, Osaka, Japan FlowPRA HLA 1) 1) 2) 2) 3) 本文 1: 日本語での投稿 words 5 79

81 MHC 2014; 21 (1) cm, ml, g, Kg, pg, µl, %, C 4. 本文 2: 英語での投稿 words 5 3 Introduction Materials and Methods Results Discussion References cm, ml, g, Kg, pg, µl, %, C 5. 引用文献 3 et al. 1 Shi Y, Yoshihara F, Nakahama H, et al.: A novel immunosuppressant FTY720 ameliorates proteinuria and aiterations of intrarenal adrenomedullin in rats with autoimune glomerulonephritis. Regulatory Peptides (127): , Tongio M, Abbal M, Bignon JD, et al.: ASH#18: HLA-DPB1. Genetic diversity of HLA Functional and Medical Implication (ed. Charron D), Medical and Scientific International Publisher, p , IVIG 1 17: 36 40, Medical View p , III. 短報 ( 研究速報, 技術速報などを含む ), 症例 1. 執筆要項 Microsoft Word Microsoft PowerPoint CD CD A 第 1 頁目 FAX 3. 本文 words IV. 総説, シリーズその他 80

82 MHC 2014; 21 (1) V. 原稿送付先 J8 MHC [email protected] Tel: Fax: 総原稿枚数図表数文献数要旨 ( 図表, 文献含む ) 原稿タイトル所属, 著者キーワード数査読著者校正原著 30 枚以内 5~10 個以内 20 個以内英文原著英文 250 words 以内和文原著英文 400 words 以内和英併記 5 個有り 1 回短報, 症例報告 15 枚以内 5 個以内 10 個以内和文英文とも英文 200 words 以内和英併記 3 個以内有り 1 回総説, その他その都度指定適宜 20 ~ 30 個前後和文 400 字以内和英併記 5 個なし 1 回 81

83 MHC 2014; 21 (1) 編集後記 HLA 日本組織適合性学会ホームページ HLA 学会事務局からのお知らせ URL URL umin.ac.jp/ [email protected] FAX [email protected] FAX [email protected] 82

Major Histocompatibility Complex 2017; 24 (3): II MHC MHC Precision Medicine HLA personalized medicine precision medicine

24 3 29 12 20 27 171 30 172 22 HLA-QC 175 30 HLA 182 183 30 HLA 190 30 192 30 HLA 194 29 HLA 196 29 HLA 198 J.J. van Rood 215 16 217 28 219 MHC 28 2 1 220 223 Major Histocompatibility Complex Official