Alterations in TCR-MHC contacts subsequent to cross-recognition of class I MHC and singly substituted peptide variants

Toshiro Ono, Teresa P. DiLorenzo, Fuming Wang, Alexis M. Kalergis, Stanley G. Nathenson

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22 Citations (Scopus)

Abstract

Vesicular stomatitis virus (VSV) elicits H-2Kb-restricted CTLs specific for the immunodominant VSV octapeptide RGYVYQGL. To study the structural features important for interaction between the TCR β-chain and the peptide/MHC complex, we immunized TCR α-chain transgenic mice with the VSV peptide and raised a panel of anti-VSV CTL clones with identical TCR α- chains. Consistent with our previous analysis of uncloned populations of primary CTLs, the anti-VSV CTL clones were all Vβ13+ and expressed TCR β- chains with highly homologous complementarity-determining region 3 (CDR3) loops. Although the clones expressed similar TCRs, they differed in their ability to cross-react with VSV peptide variants singly substituted at TCR contact positions 4 and 6. These findings allowed us to identify short stretches of amino acids in the C-terminal region of the CDR3β loop that, when altered, modify the cross-reaction capability of the TCR to position 4 and position 6 variant peptides. To further probe the structural correlates of biologic cross-reactivity, we used cross-reactive CTL clones and cell lines expressing point mutations in H-2K(b) to investigate the effect of single amino acid changes in the peptide on the pattern of recognition of the TCR for the peptide/MHC complex. Single conservative substitutions in the peptide were sufficient to alter the recognition contacts between a cross- reactive TCR and the MHC molecule, supporting the idea that the TCR can make overall structural adjustments in MHC contacts to accommodate single amino acid changes in the peptide.

Original languageEnglish
Pages (from-to)5454-5463
Number of pages10
JournalJournal of Immunology
Volume161
Issue number10
Publication statusPublished - Nov 15 1998

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Ono, T., DiLorenzo, T. P., Wang, F., Kalergis, A. M., & Nathenson, S. G. (1998). Alterations in TCR-MHC contacts subsequent to cross-recognition of class I MHC and singly substituted peptide variants. Journal of Immunology, 161(10), 5454-5463.