4JRX

Crystal Structure of CA5 TCR-HLA B*3505-LPEP complex

4JRX の概要

• エントリーDOI: 10.2210/pdb4jrx/pdb
• 関連するPDBエントリー: 4JRY
• 分子名称: MHC class I antigen, Beta-2-microglobulin, Trans-activator protein BZLF1, ... (8 entities in total)
• 機能のキーワード: tcr, t cell, hla b*3508, lpep, ebv, alloreactivity, 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 : Q3KSS8
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 96351.70

構造登録者

Liu, Y.C.,Rossjohn, J.,Gras, S. (登録日: 2013-03-22, 公開日: 2013-04-10, 最終更新日: 2024-10-16)

主引用文献

Liu, Y.C.,Miles, J.J.,Neller, M.A.,Gostick, E.,Price, D.A.,Purcell, A.W.,McCluskey, J.,Burrows, S.R.,Rossjohn, J.,Gras, S.
Highly divergent T-cell receptor binding modes underlie specific recognition of a bulged viral peptide bound to a human leukocyte antigen class I molecule.
J.Biol.Chem., 288:15442-15454, 2013

PubMed Abstract: Human leukocyte antigen (HLA)-I molecules can present long peptides, yet the mechanisms by which T-cell receptors (TCRs) recognize featured pHLA-I landscapes are unclear. We compared the binding modes of three distinct human TCRs, CA5, SB27, and SB47, complexed with a "super-bulged" viral peptide (LPEPLPQGQLTAY) restricted by HLA-B*35:08. The CA5 and SB27 TCRs engaged HLA-B*35:08(LPEP) similarly, straddling the central region of the peptide but making limited contacts with HLA-B*35:08. Remarkably, the CA5 TCR did not contact the α1-helix of HLA-B*35:08. Differences in the CDR3β loop between the CA5 and SB27 TCRs caused altered fine specificities. Surprisingly, the SB47 TCR engaged HLA-B*35:08(LPEP) using a completely distinct binding mechanism, namely "bypassing" the bulged peptide and making extensive contacts with the extreme N-terminal end of HLA-B*35:08. This docking footprint included HLA-I residues not observed previously as TCR contact sites. The three TCRs exhibited differing patterns of alloreactivity toward closely related or distinct HLA-I allotypes. Thus, the human T-cell repertoire comprises a range of TCRs that can interact with "bulged" pHLA-I epitopes using unpredictable strategies, including the adoption of atypical footprints on the MHC-I.

PubMed: 23569211
DOI: 10.1074/jbc.M112.447185

実験手法

X-RAY DIFFRACTION (2.3 Å)