7R7W

Crystal structure of HLA-B*5301 complex with an HIV-1 Gag-derived epitope QW9 S3T variant

7R7W の概要

• エントリーDOI: 10.2210/pdb7r7w/pdb
• 分子名称: MHC class I antigen, Beta-2-microglobulin, GLN-ALA-THR-GLN-GLU-VAL-LYS-ASN-TRP, ... (4 entities in total)
• 機能のキーワード: mhc, t cell immunity, antigen presentation, hiv, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 45240.19

構造登録者

Li, X.L.,Tan, K.M.,Walker, B.D.,Wang, J.H. (登録日: 2021-06-25, 公開日: 2022-06-29, 最終更新日: 2024-11-13)

主引用文献

Li, X.,Singh, N.K.,Collins, D.R.,Ng, R.,Zhang, A.,Lamothe-Molina, P.A.,Shahinian, P.,Xu, S.,Tan, K.,Piechocka-Trocha, A.,Urbach, J.M.,Weber, J.K.,Gaiha, G.D.,Takou Mbah, O.C.,Huynh, T.,Cheever, S.,Chen, J.,Birnbaum, M.,Zhou, R.,Walker, B.D.,Wang, J.H.
Molecular basis of differential HLA class I-restricted T cell recognition of a highly networked HIV peptide.
Nat Commun, 14:2929-2929, 2023

PubMed Abstract: Cytotoxic-T-lymphocyte (CTL) mediated control of HIV-1 is enhanced by targeting highly networked epitopes in complex with human-leukocyte-antigen-class-I (HLA-I). However, the extent to which the presenting HLA allele contributes to this process is unknown. Here we examine the CTL response to QW9, a highly networked epitope presented by the disease-protective HLA-B57 and disease-neutral HLA-B53. Despite robust targeting of QW9 in persons expressing either allele, T cell receptor (TCR) cross-recognition of the naturally occurring variant QW9_S3T is consistently reduced when presented by HLA-B53 but not by HLA-B57. Crystal structures show substantial conformational changes from QW9-HLA to QW9_S3T-HLA by both alleles. The TCR-QW9-B53 ternary complex structure manifests how the QW9-B53 can elicit effective CTLs and suggests sterically hindered cross-recognition by QW9_S3T-B53. We observe populations of cross-reactive TCRs for B57, but not B53 and also find greater peptide-HLA stability for B57 in comparison to B53. These data demonstrate differential impacts of HLAs on TCR cross-recognition and antigen presentation of a naturally arising variant, with important implications for vaccine design.

PubMed: 37217466
DOI: 10.1038/s41467-023-38573-8

実験手法

X-RAY DIFFRACTION (1.17 Å)