Specific prolongation of allograft survival by a T-cell-receptor-derived peptide

Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):9872-6. doi: 10.1073/pnas.90.21.9872.

Abstract

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.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Female
  • Graft Survival / drug effects*
  • Graft Survival / immunology
  • Haplotypes
  • Histocompatibility Antigens Class I / immunology
  • Histocompatibility Antigens Class II / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • Molecular Sequence Data
  • Peptide Fragments / pharmacology*
  • Receptors, Antigen, T-Cell / immunology*
  • Skin Transplantation / immunology*
  • T-Lymphocytes, Cytotoxic / immunology
  • Transplantation, Homologous / immunology

Substances

  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II
  • Peptide Fragments
  • Receptors, Antigen, T-Cell