Peptide-induced changes in class I heavy chains alter allorecognition

J. A. Bluestone, A. Kaliyaperumal, S. Jameson, S. Miller, R. Dick

Research output: Contribution to journalArticlepeer-review

69 Scopus citations


Class I molecules of the MHC are intimately involved in the development and function of CD8+ T cells. Small peptides, derived from endogenous proteins, bind within the Ag binding groove created by the β-pleated sheets and α-helices of the α1 and α2 domains of the class I molecule. This peptide-MHC complex has been shown to influence allorecognition by CD8+ T cells. However, the precise role of peptide in alloantigen recognition remains unclear. We have previously shown that conformational changes induced in the class I molecules can be identified as specific alterations in serologic epitopes. These results suggested that alloreactive T cells may detect structural changes in MHC based on the nature of the peptide binding to the class I protein. Here, we have shown that, in at least some instances, alloreactivity may not depend on the recognition of a precise self-peptide but on an epitope on the class I molecule influenced by the peptide. The nature of specific peptides expressed by class I-bearing cells may, therefore, have a dramatic effect on T cell development, self-tolerance, and alloreactivity.

Original languageEnglish (US)
Pages (from-to)3943-3953
Number of pages11
JournalJournal of Immunology
Issue number8
StatePublished - 1993


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