6Z9V

Human Class I Major Histocompatibility Complex, A02 allele, presenting IIGWMWIPV

6Z9V の概要

• エントリーDOI: 10.2210/pdb6z9v/pdb
• 分子名称: MHC class I antigen, CALCIUM ION, Beta-2-microglobulin, ... (11 entities in total)
• 機能のキーワード: mhc i, immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 92205.60

構造登録者

Rizkallah, P.J.,Man, S.,Redman, J.E. (登録日: 2020-06-04, 公開日: 2021-06-30, 最終更新日: 2024-11-13)

主引用文献

Man, S.,Redman, J.E.,Cross, D.L.,Cole, D.K.,Can, I.,Davies, B.,Hashimdeen, S.S.,Reid, R.,Llewellyn-Lacey, S.,Miners, K.L.,Ladell, K.,Lissina, A.,Brown, P.E.,Wooldridge, L.,Price, D.A.,Rizkallah, P.J.
Synthetic Peptides with Inadvertent Chemical Modifications Can Activate Potentially Autoreactive T Cells.
J Immunol., 207:1009-1017, 2021

PubMed Abstract: The human CD8 T cell clone 6C5 has previously been shown to recognize the -butyl-modified Bax peptide LLSY(3-Bu)FGTPT presented by HLA-A*02:01. This nonnatural epitope was likely created as a by-product of fluorenylmethoxycarbonyl protecting group peptide synthesis and bound poorly to HLA-A*02:01. In this study, we used a systematic approach to identify and characterize natural ligands for the 6C5 TCR. Functional analyses revealed that 6C5 T cells only recognized the LLSYFGTPT peptide when Bu was added to the tyrosine residue and did not recognize the LLSYFGTPT peptide modified with larger (di-Bu) or smaller chemical groups (Me). Combinatorial peptide library screening further showed that 6C5 T cells recognized a series of self-derived peptides with dissimilar amino acid sequences to LLSY(3-Bu)FGTPT. Structural studies of LLSY(3-Bu)FGTPT and two other activating nonamers (IIGWMWIPV and LLGWVFAQV) in complex with HLA-A*02:01 demonstrated similar overall peptide conformations and highlighted the importance of the position (P) 4 residue for T cell recognition, particularly the capacity of the bulky amino acid tryptophan to substitute for the Bu-modified tyrosine residue in conjunction with other changes at P5 and P6. Collectively, these results indicated that chemical modifications directly altered the immunogenicity of a synthetic peptide via molecular mimicry, leading to the inadvertent activation of a T cell clone with unexpected and potentially autoreactive specificities.

PubMed: 34321228
DOI: 10.4049/jimmunol.2000756

実験手法

X-RAY DIFFRACTION (2.01 Å)