PEPTIDE-INDUCED CHANGES IN CLASS-I HEAVY-CHAINS ALTER ALLORECOGNITION

Class I molecules of the MHC are intimately involved in the developmen t and function of CD8+ T cells. Small peptides, derived from endogenou s proteins, bind within the Ag binding groove created by the beta-plea ted sheets and alpha-helices of the alpha1 and alpha2 domains of the c lass 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 t hat conformational changes induced in the class I molecules can be ide ntified as specific alterations in serologic epitopes. These results s uggested that alloreactive T cells may detect structural changes in MH C based on the nature of the peptide binding to the class I protein. H ere, we have shown that, in at least some instances, alloreactivity ma y not depend on the recognition of a precise self-peptide but on an ep itope 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 allo reactivity.