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 β8 variable region that predominates in responses to Ldwas tested. This V β8-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 β8+effector cells nor does the Vβ8 peptide bind to the Ldligand binding cleft. We propose that this peptide functions as an antagonist, competing with the native TCR for recognition of the Ldmolecule.