4XXC

HLA-B*1801 in complex with a self-peptide, DELEIKAY

4XXC の概要

• エントリーDOI: 10.2210/pdb4xxc/pdb
• 関連するPDBエントリー: 4JQV
• 分子名称: HLA class I histocompatibility antigen, B-18 alpha chain, Beta-2-microglobulin, ASP-GLU-LEU-GLU-ILE-LYS-ALA-TYR, ... (5 entities in total)
• 機能のキーワード: ebv, hla, tcr, cross-reactivity, immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Membrane; Single-pass type I membrane protein: P30466; Secreted : P61769
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 44969.66

構造登録者

Hibbert, K.M.,Rossjohn, J.,Gras, S. (登録日: 2015-01-30, 公開日: 2015-04-08, 最終更新日: 2023-09-27)

主引用文献

Rist, M.J.,Hibbert, K.M.,Croft, N.P.,Smith, C.,Neller, M.A.,Burrows, J.M.,Miles, J.J.,Purcell, A.W.,Rossjohn, J.,Gras, S.,Burrows, S.R.
T Cell Cross-Reactivity between a Highly Immunogenic EBV Epitope and a Self-Peptide Naturally Presented by HLA-B*18:01+ Cells.
J Immunol., 194:4668-4675, 2015

PubMed Abstract: T cell cross-reactivity underpins the molecular mimicry hypothesis in which microbial peptides sharing structural features with host peptides stimulate T cells that cross-react with self-peptides, thereby initiating and/or perpetuating autoimmune disease. EBV represents a potentially important factor in the pathogenesis of several T cell-mediated autoimmune disorders, with molecular mimicry a likely mechanism. In this study, we describe a human self-peptide (DELEIKAY) that is a homolog of a highly immunogenic EBV T cell epitope (SELEIKRY) presented by HLA-B*18:01. This self-peptide was shown to bind stably to HLA-B*18:01, and peptide elution/mass spectrometric studies showed it is naturally presented by this HLA molecule on the surface of human cells. A significant proportion of CD8(+) T cells raised from some healthy individuals against this EBV epitope cross-reacted with the self-peptide. A diverse array of TCRs was expressed by the cross-reactive T cells, with variable functional avidity for the self-peptide, including some T cells that appeared to avoid autoreactivity by a narrow margin, with only 10-fold more of the self-peptide required for equivalent activation as compared with the EBV peptide. Structural studies revealed that the self-peptide-HLA-B*18:01 complex is a structural mimic of the EBV peptide-HLA-B*18:01 complex, and that the strong antiviral T cell response is primarily dependent on the alanine/arginine mismatch at position 7. To our knowledge, this is the first report confirming the natural presentation of a self-peptide cross-recognized in the context of self-HLA by EBV-reactive CD8(+) T cells. These results illustrate how aberrant immune responses and immunopathological diseases could be generated by EBV infection.

PubMed: 25855358
DOI: 10.4049/jimmunol.1500233

実験手法

X-RAY DIFFRACTION (1.426 Å)