4PRD

Crystal structure of a HLA-B*35:08-HPVG-D5

4PRD の概要

• エントリーDOI: 10.2210/pdb4prd/pdb
• 関連するPDBエントリー: 2FYY 3VM7 4PR5 4PRA 4PRB 4PRE 4PRH 4PRI 4PRN 4PRP
• 分子名称: MHC class I antigen, Beta-2-microglobulin, Epstein-Barr nuclear antigen 1, ... (5 entities in total)
• 機能のキーワード: human leukocyte antigen class i, epstein-barr virus, viral escape, t cell receptor, viral immunity, immune system
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Secreted . Note=(Microbial infection) In the presence of M: P61769; Host nucleus : Q3KSS4
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 45104.83

構造登録者

Yu Chih, L.,Rossjohn, J.,Gras, S. (登録日: 2014-03-05, 公開日: 2014-04-16, 最終更新日: 2024-10-16)

主引用文献

Liu, Y.C.,Chen, Z.,Neller, M.A.,Miles, J.J.,Purcell, A.W.,McCluskey, J.,Burrows, S.R.,Rossjohn, J.,Gras, S.
A Molecular Basis for the Interplay between T Cells, Viral Mutants, and Human Leukocyte Antigen Micropolymorphism.
J.Biol.Chem., 289:16688-16698, 2014

PubMed Abstract: Mutations within T cell epitopes represent a common mechanism of viral escape from the host protective immune response. The diverse T cell repertoire and the extensive human leukocyte antigen (HLA) polymorphism across populations is the evolutionary response to viral mutation. However, the molecular basis underpinning the interplay between HLA polymorphism, the T cell repertoire, and viral escape is unclear. Here we investigate the T cell response to a HLA-B*35:01- and HLA-B*35:08-restricted (407)HPVGEADYFEY(417) epitope from Epstein-Barr virus and naturally occurring variants at positions 4 and 5 thereof. Each viral variant differently impacted on the epitope's flexibility and conformation when bound to HLA-B*35:08 or HLA-B*35:01. We provide a molecular basis for understanding how the single residue polymorphism that discriminates between HLA-B*35:01/08 profoundly impacts on T cell receptor recognition. Surprisingly, one viral variant (P5-Glu to P5-Asp) effectively changed restriction preference from HLA-B*35:01 to HLA-B*35:08. Collectively, our study portrays the interplay between the T cell response, viral escape, and HLA polymorphism, whereby HLA polymorphism enables altered presentation of epitopes from different strains of Epstein-Barr virus.

PubMed: 24759101
DOI: 10.1074/jbc.M114.563502

実験手法

X-RAY DIFFRACTION (1.75 Å)