Peptide-induced changes in class I heavy chains alter allorecognition.
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 beta-pleated sheets and alpha-helices of the alpha 1 and alpha 2 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.
Bluestone
J A
JA
Ben May Institute, Department of Pathology, University of Chicago, IL 60637.
Kaliyaperumal
A
A
Jameson
S
S
Miller
S
S
Dick
R
R
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D006183:H-2 Antigens / Q000032:analysis; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology*; D011487:Protein Conformation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D015395:Histocompatibility Antigens Class I; D010455:Peptides