Functional avidity of tumor antigen-specific CTL recognition directly correlates with the stability of MHC/peptide multimer binding to TCR

J Immunol. 2002 Feb 1;168(3):1167-71. doi: 10.4049/jimmunol.168.3.1167.

Abstract

Avidity of Ag recognition by tumor-specific T cells is one of the main parameters that determines the potency of a tumor rejection Ag. In this study we show that the relative efficiency of staining of tumor Ag-specific T lymphocytes with the corresponding fluorescent MHC class I/peptide multimeric complexes can considerably vary with staining conditions and does not necessarily correlate with avidity of Ag recognition. Instead, we found a clear correlation between avidity of Ag recognition and the stability of MHC class I/peptide multimeric complexes interaction with TCR as measured in dissociation kinetic experiments. These findings are relevant for both identification and isolation of tumor-reactive CTL.

MeSH terms

  • Antigens, Neoplasm / immunology
  • Antigens, Neoplasm / metabolism*
  • Clone Cells
  • Cytotoxicity Tests, Immunologic / methods
  • Cytotoxicity, Immunologic*
  • Epitopes, T-Lymphocyte / immunology
  • Epitopes, T-Lymphocyte / metabolism*
  • Flow Cytometry / methods
  • HLA-A2 Antigen / immunology
  • HLA-A2 Antigen / metabolism*
  • Humans
  • Kinetics
  • Peptide Fragments / immunology
  • Peptide Fragments / metabolism*
  • Protein Binding / immunology
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Antigen, T-Cell / metabolism*
  • Staining and Labeling
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / metabolism*
  • Tumor Cells, Cultured

Substances

  • Antigens, Neoplasm
  • Epitopes, T-Lymphocyte
  • HLA-A2 Antigen
  • Peptide Fragments
  • Receptors, Antigen, T-Cell