Specific prolongation of allograft survival by a T-cell-receptor-derived peptide.
Allograft rejection results from the specific recognition by host CD8+ T cells of allogeneic major histocompatibility complex (MHC) molecules on the tissue graft. The specificity of this cellular response is determined by the molecular interaction of the T-cell receptor (TCR) on host T cells with the MHC molecule and its bound ligand on the grafted tissue. To better understand the precise manner by which the TCR interacts with the MHC-peptide complex and how to therapeutically intervene, we have studied the allogeneic response to the mouse class I MHC molecule Ld. In this report, the therapeutic potential of a synthetic peptide derived from the TCR V beta 8 variable region that predominates in responses to Ld was tested. This V beta 8-derived peptide was found to dramatically and specifically block the in vivo and in vitro allogeneic response to Ld. Furthermore, this specific blocking is not dependent upon the presence of V beta 8+ effector cells nor does the V beta 8 peptide bind to the Ld ligand binding cleft. We propose that this peptide functions as an antagonist, competing with the native TCR for recognition of the Ld molecule.
Goss
J A
JA
Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110.
Alexander-Miller
M A
MA
Gorka
J
J
Flye
M W
MW
Connolly
J M
JM
Hansen
T H
TH
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D005260:Female; D006085:Graft Survival / Q000187:drug effects* / Q000276:immunology; D006239:Haplotypes; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D016038:Skin Transplantation / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014184:Transplantation, Homologous / Q000276:immunology
D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell