5NMF

868 TCR in complex with HLA A02 presenting SLYNTIATL

5NMF の概要

• エントリーDOI: 10.2210/pdb5nmf/pdb
• 分子名称: HLA class I histocompatibility antigen, A-2 alpha chain, Beta-2-microglobulin, Gag protein, ... (10 entities in total)
• 機能のキーワード: mhc, tcr, cd8+, 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: P01892; Secreted . Note=(Microbial infection) In the presence of M: P61769
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 191226.26

構造登録者

Rizkallah, P.J.,Cole, D.K.,Fuller, A.,Sewell, A.K. (登録日: 2017-04-05, 公開日: 2017-11-15, 最終更新日: 2024-10-09)

主引用文献

Cole, D.K.,Fuller, A.,Dolton, G.,Zervoudi, E.,Legut, M.,Miles, K.,Blanchfield, L.,Madura, F.,Holland, C.J.,Bulek, A.M.,Bridgeman, J.S.,Miles, J.J.,Schauenburg, A.J.A.,Beck, K.,Evavold, B.D.,Rizkallah, P.J.,Sewell, A.K.
Dual Molecular Mechanisms Govern Escape at Immunodominant HLA A2-Restricted HIV Epitope.
Front Immunol, 8:1503-1503, 2017

PubMed Abstract: Serial accumulation of mutations to fixation in the SLYNTVATL (SL9) immunodominant, HIV p17 Gag-derived, HLA A2-restricted cytotoxic T lymphocyte epitope produce the SLFNTIAVL triple mutant "ultimate" escape variant. These mutations in solvent-exposed residues are believed to interfere with TCR recognition, although confirmation has awaited structural verification. Here, we solved a TCR co-complex structure with SL9 and the triple escape mutant to determine the mechanism of immune escape in this eminent system. We show that, in contrast to prevailing hypotheses, the main TCR contact residue is 4N and the dominant mechanism of escape is not lack of TCR engagement. Instead, mutation of solvent-exposed residues in the peptide destabilise the peptide-HLA and reduce peptide density at the cell surface. These results highlight the extraordinary lengths that HIV employs to evade detection by high-affinity TCRs with a broad peptide-binding footprint and necessitate re-evaluation of this exemplar model of HIV TCR escape.

PubMed: 29209312
DOI: 10.3389/fimmu.2017.01503

実験手法

X-RAY DIFFRACTION (2.89 Å)