Alloreactive T cells discriminate among a diverse set of endogenous peptides

William R. Heath, Kevin P. Kane, Matthew F. Mescher, Linda A. Sherman

Research output: Contribution to journalArticle

117 Scopus citations

Abstract

Previous studies have demonstrated that class I major histocompatibility complex (MHC) molecules are occupied by peptides of endogenously synthesized self proteins. Since graft rejection appears to be mediated by the normal occurrence of high frequencies of cytolytic T lymphocytes (CTLs) specific for allogeneic MHC molecules, it is important to know if such CTLs recognize specific MHC-peptide complexes (as opposed to the MHC molecule per se) and, if so, whether allorecognition is the result of the recognition of a limited spectrum of antigenic determinants or, alternatively, the recognition of a diverse array of MHC-self peptide complexes. This issue has been examined using a mutant cell line, T2Kb, that expresses class I molecules devoid of endogenously derived peptides. This cell line was not recognized by Kb-specific alloreactive CTLs. However, upon exposure to peptides derived by cyanogen bromide cleavage of cytoplasmic proteins these cells became sensitized for recognition and lysis by a majority of the CTL clones examined. Reverse-phase HPLC fractionation of the heterogeneous cell-derived peptides revealed that individual CTL clones were specific for different peptide antigen(s). Thus, the high frequency of alloreactive T cells that is responsible for graft rejection appears to represent the sum of numerous T-cell clones specific for a diverse array of endogenous peptide antigens presented in the context of allogeneic class I molecules.

Original languageEnglish (US)
Pages (from-to)5101-5105
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume88
Issue number12
DOIs
StatePublished - Jun 15 1991

Keywords

  • Class I major histocompatibility molecules
  • Cytotoxic T lymphocytes
  • Graft rejection

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