A cytotoxic T lymphocyte clone can recognize the same naturally occurring self peptide in association with a self and nonself class I MHC protein

Mol Immunol. 1994 Sep;31(13):967-75. doi: 10.1016/0161-5890(94)90091-4.

Abstract

The alloreactive CD8+ cytotoxic T lymphocyte (CTL) clone 2C was previously shown to recognize complexes made up of the class I MHC (MHC-I) molecule Ld and an octapeptide (LSPFPFDL, termed p2Ca) isolated from tissues of H-2d mice. Because peptide p2Ca has also been found in BALB.B (H-2b) mice, the strain from which clone 2C originated, the question arises as to whether these T cells can recognize peptide p2Ca in association with a self MHC protein of the H-2b haplotype. Here we show that 2C CTL do indeed recognize peptide p2Ca in association with Kb on the surface of H-2b cells or on transfected cells expressing Kb, but that an approximately 1000-fold higher concentration of this peptide is required to sensitize Kb+ than Ld+ target cells for lysis by 2C cells. However, the peptide's binding to Kb was not much weaker than to Ld, with only an approximately 10-fold difference in the respective equilibrium constants. These results predict that the T cell receptor (TcR) of clone 2C has a much lower intrinsic affinity for p2Ca-Kb complexes than for p2Ca-Ld complexes, and they provide some quantitative limits on the requirements for triggering T cell-mediated autoimmune reactivity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Autoimmunity / immunology*
  • Binding, Competitive
  • Cell Line
  • Clone Cells
  • Cytotoxicity Tests, Immunologic
  • Flow Cytometry
  • Histocompatibility Antigens Class I / genetics*
  • Humans
  • Mice
  • Molecular Sequence Data
  • Oligopeptides / immunology*
  • T-Lymphocytes, Cytotoxic / immunology*

Substances

  • Histocompatibility Antigens Class I
  • Oligopeptides
  • p2Ca peptide