1T22

Structural basis for degenerate recognition of HIV peptide variants by cytotoxic lymphocyte, variant SL9, orthorhombic crystal

1T22 の概要

• エントリーDOI: 10.2210/pdb1t22/pdb
• 関連するPDBエントリー: 1s8d 1t1w 1t1x 1t1y 1t1z 1t20 1t21
• 分子名称: HLA class I histocompatibility antigen, A-2 alpha chain, Beta-2-microglobulin, GAG PEPTIDE, ... (4 entities in total)
• 機能のキーワード: ctl, cytotoxic t lymphocytes, hiv, human immunodeficiency virus, mhc, major histocompatibility complex, pmhc, peptide mhc complex, rmsd, root-mean-squared deviation, siv, simian immunodeficiency virus, tcr, t-cell receptor, 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: P01884
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 44583.46

構造登録者

Martinez-Hackert, E.,Anikeeva, N.,Kalams, S.A.,Walker, B.D.,Hendrickson, W.A.,Sykulev, Y. (登録日: 2004-04-19, 公開日: 2005-09-06, 最終更新日: 2024-10-30)

主引用文献

Martinez-Hackert, E.,Anikeeva, N.,Kalams, S.A.,Walker, B.D.,Hendrickson, W.A.,Sykulev, Y.
Structural Basis for Degenerate Recognition of Natural HIV Peptide Variants by Cytotoxic Lymphocytes.
J.Biol.Chem., 281:20205-20212, 2006

PubMed Abstract: It is well established that even small changes in amino acid side chains of antigenic peptide bound to major histocompatibility complex (MHC) protein may completely abrogate recognition of the peptide-MHC (pMHC) complex by the T cell receptor (TCR). Often, however, several nonconservative substitutions in the peptide antigen are accommodated and do not impair its recognition by TCR. For example, a preponderance of natural sequence variants of the human immunodeficiency virus p17 Gag-derived peptide SLYNTVATL (SL9) are recognized by cytotoxic T lymphocytes, which implies that interactions with SL9 variants are degenerate both with respect to the class I MHC molecule and with respect to TCR. Here we study the molecular basis for this degenerate recognition of SL9 variants. We show that several SL9 variants bind comparably well to soluble HLA-A2 and to a particular soluble TCR and that these variants are active in the cognate cytotoxicity assay. Natural SL9 variation is restricted by its context in the HIV p17 matrix protein. High resolution crystal structures of seven selected SL9 variants bound to HLA-A2 all have remarkably similar peptide conformations and side-chain dispositions outside sites of substitution. This preservation of the peptide conformation despite epitope variations suggests a mechanism for the observed degeneracy in pMHC recognition by TCR and may contribute to the persistence of SL9-mediated immune responses in chronically infected individuals.

PubMed: 16702212
DOI: 10.1074/jbc.M601934200

実験手法

X-RAY DIFFRACTION (2.2 Å)