Differential binding of a minor histocompatibility antigen peptide to H-2 class I molecules correlates with immune responsiveness

P. J. Wettstein, G. M. Van Bleek, S. G. Nathenson

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Minor histocompatibility (H) Ag are recognized in the context of MHC class I (K/D) molecules and can constitute a strong barrier to tissue transplantation. The products encoded by the MHC (H-2 in mice) have been shown recently to be Ag-presenting molecules that bind foreign and self peptides in their peptide binding sites. Different class I molecules preferentially bind different arrays of endogenous peptides for presentation to CTL. Previous studies showed that the Kb-restricted CTL response to one minor histocompatibility Ag, H-4, varied in different Kb mutants. One possible basis for this variation might be that the response is regulated by the level of binding of an H-4 peptide by class I molecules. To analyze this possibility, we initiated studies to identify the H-4 peptide that is included in the array of self peptides. The complete mixture of peptides eluted from Kb molecules of H-4+ tumor cells was able to sensitize H-4- targets for lysis by H-4-specific CTL. The presence of a specific H-4 peptide was confirmed when the radiolabeled peptide mix eluted from Kb molecules was separated by HPLC. Only one peak in the profile of H-4+ tumor peptides was capable of sensitizing H-4- targets for lysis by H-4-specific CTL; this active peak was absent in H-4 mutant cells. Peptide mixtures eluted from a panel of Kb mutant molecules extracted from H-4+ lymphocytes varied in their capacities to sensitize targets for H-4-specific lysis and the relative sensitization correlated with the demonstrated capacity of mutant mice to generate H-4-specific CTL. Therefore, the highly specific genetic control of the T cell response to the H-4 minor histocompatibility Ag appears to be due to the differential binding of an H-4 peptide by class I molecules.

Original languageEnglish (US)
Pages (from-to)2753-2760
Number of pages8
JournalJournal of Immunology
Volume150
Issue number7
StatePublished - 1993

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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