PMID- 31396224 OWN - NLM STAT- MEDLINE DCOM- 20201110 LR - 20201110 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 10 DP - 2019 TI - Divergent Peptide Presentations of HLA-A(*)30 Alleles Revealed by Structures With Pathogen Peptides. PG - 1709 LID - 10.3389/fimmu.2019.01709 [doi] LID - 1709 AB - Human leukocyte antigen (HLA) alleles have a high degree of polymorphism, which determines their peptide-binding motifs and subsequent T-cell receptor recognition. The simplest way to understand the cross-presentation of peptides by different alleles is to classify these alleles into supertypes. A1 and A3 HLA supertypes are widely distributed in humans. However, direct structural and functional evidence for peptide presentation features of key alleles (e.g., HLA-A(*)30:01 and -A(*)30:03) are lacking. Herein, the molecular basis of peptide presentation of HLA-A(*)30:01 and -A(*)30:03 was demonstrated by crystal structure determination and thermostability measurements of complexes with T-cell epitopes from influenza virus (NP44), human immunodeficiency virus (RT313), and Mycobacterium tuberculosis (MTB). When binding to the HIV peptide, RT313, the POmega-Lys anchoring modes of HLA-A(*)30:01, and -A(*)30:03 were similar to those of HLA-A(*)11:01 in the A3 supertype. However, HLA-A(*)30:03, but not -A(*)30:01, also showed binding with the HLA(*)01:01-favored peptide, NP44, but with a specific structural conformation. Thus, different from our previous understanding, HLA-A(*)30:01 and -A(*)30:03 have specific peptide-binding characteristics that may lead to their distinct supertype-featured binding peptide motifs. Moreover, we also found that residue 77 in the F pocket was one of the key residues for the divergent peptide presentation characteristics of HLA-A(*)30:01 and -A(*)30:03. Interchanging residue 77 between HLA-A(*)30:01 and HLA-A(*)30:03 switched their presented peptide profiles. Our results provide important recommendations for screening virus and tumor-specific peptides among the population with prevalent HLA supertypes for vaccine development and immune interventions. FAU - Zhu, Shiyan AU - Zhu S AD - School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China. AD - NHC Key Laboratory of Medical Virology and Viral Diseases, Chinese Center for Disease Control and Prevention, National Institute for Viral Disease Control and Prevention, Beijing, China. FAU - Liu, Kefang AU - Liu K AD - NHC Key Laboratory of Medical Virology and Viral Diseases, Chinese Center for Disease Control and Prevention, National Institute for Viral Disease Control and Prevention, Beijing, China. AD - Faculty of Health Sciences, University of Macau, Macau, China. FAU - Chai, Yan AU - Chai Y AD - CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China. FAU - Wu, Yanan AU - Wu Y AD - School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China. AD - NHC Key Laboratory of Medical Virology and Viral Diseases, Chinese Center for Disease Control and Prevention, National Institute for Viral Disease Control and Prevention, Beijing, China. FAU - Lu, Dan AU - Lu D AD - NHC Key Laboratory of Medical Virology and Viral Diseases, Chinese Center for Disease Control and Prevention, National Institute for Viral Disease Control and Prevention, Beijing, China. FAU - Xiao, Wenling AU - Xiao W AD - School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China. AD - NHC Key Laboratory of Medical Virology and Viral Diseases, Chinese Center for Disease Control and Prevention, National Institute for Viral Disease Control and Prevention, Beijing, China. FAU - Cheng, Hao AU - Cheng H AD - Beijing Institutes of Life Science, University of Chinese Academy of Sciences, Beijing, China. FAU - Zhao, Yingze AU - Zhao Y AD - NHC Key Laboratory of Medical Virology and Viral Diseases, Chinese Center for Disease Control and Prevention, National Institute for Viral Disease Control and Prevention, Beijing, China. FAU - Ding, Chunming AU - Ding C AD - School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China. FAU - Lyu, Jianxin AU - Lyu J AD - School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China. AD - Hangzhou Medical College, Hangzhou, China. FAU - Lou, Yongliang AU - Lou Y AD - School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China. FAU - Gao, George F AU - Gao GF AD - School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China. AD - NHC Key Laboratory of Medical Virology and Viral Diseases, Chinese Center for Disease Control and Prevention, National Institute for Viral Disease Control and Prevention, Beijing, China. AD - CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China. AD - Beijing Institutes of Life Science, University of Chinese Academy of Sciences, Beijing, China. FAU - Liu, William J AU - Liu WJ AD - School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China. AD - NHC Key Laboratory of Medical Virology and Viral Diseases, Chinese Center for Disease Control and Prevention, National Institute for Viral Disease Control and Prevention, Beijing, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190723 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (Epitopes, T-Lymphocyte) RN - 0 (HLA-A Antigens) RN - 0 (HLA-A*30 antigen) RN - 0 (Peptides) SB - IM MH - Antigen Presentation/*immunology MH - Cross-Priming/*immunology MH - Epitopes, T-Lymphocyte/*immunology MH - HIV/immunology MH - HLA-A Antigens/chemistry/*immunology MH - Humans MH - Lymphocyte Activation/*immunology MH - Mycobacterium tuberculosis/immunology MH - Orthomyxoviridae/immunology MH - Peptides/immunology PMC - PMC6664060 OTO - NOTNLM OT - HLA superfamily OT - HLA-A3 OT - Mycobacterium tuberculosis OT - T-cell OT - cross-presentation OT - human immunodeficiency virus (HIV) OT - influenza virus OT - major histocompatibility complex (MHC) EDAT- 2019/08/10 06:00 MHDA- 2020/11/11 06:00 PMCR- 2019/01/01 CRDT- 2019/08/10 06:00 PHST- 2019/01/31 00:00 [received] PHST- 2019/07/08 00:00 [accepted] PHST- 2019/08/10 06:00 [entrez] PHST- 2019/08/10 06:00 [pubmed] PHST- 2020/11/11 06:00 [medline] PHST- 2019/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2019.01709 [doi] PST - epublish SO - Front Immunol. 2019 Jul 23;10:1709. doi: 10.3389/fimmu.2019.01709. eCollection 2019.