A cluster of mutations in HLA-A2 α2 helix abolishes peptide recognition by T cells

Robert J. Moots, Masanori Matsui, Laszlo Pazmany, Andrew J. McMichael, Jeffrey A. Frelinger

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

In order to investigate the regions of HLA-A2 that control peptide-specific cytotoxic T lymphocyte (CTL) recognition, 37 HLA-A2 genes coding for 50 point mutations that span the α2 helix were synthesized by the technique of saturation mutagenesis. Twenty-nine of these genes, which code for 41 point mutations, were transfected into C1R cells and used as targets in cytotoxicity assays, in the presence of influenza-A matrix peptide 58-68 with specific CTL as effectors. All the transfectants were recognized fully by matrix peptide-specific CTL apart from those with amino acid substitutions at positions 152, 154, 155, 156, or 161, which led to a total loss of recognition and those with mutations at residue 27 or a double mutation at 138 and 150, which were recognized in an intermediate manner. The clustering of the crucial residues that emerges may reflect direct interaction of their side-chains with peptide or the CTL receptor.

Original languageEnglish (US)
Pages (from-to)141-148
Number of pages8
JournalImmunogenetics
Volume34
Issue number3
DOIs
StatePublished - Sep 1991

ASJC Scopus subject areas

  • Immunology
  • Genetics

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