Relationship between CD8-dependent antigen recognition, T cell functional avidity, and tumor cell recognition

Cancer Immunol Immunother. 2009 May;58(5):719-28. doi: 10.1007/s00262-008-0594-2. Epub 2008 Oct 3.

Abstract

Effective immunotherapy using T cell receptor (TCR) gene-modified T cells requires an understanding of the relationship between TCR affinity and functional avidity of T cells. In this study, we evaluate the relative affinity of two TCRs isolated from HLA-A2-restricted, gp100-reactive T cell clones with extremely high functional avidity. Furthermore, one of these T cell clones, was CD4- CD8- indicating that antigen recognition by this clone was CD8 independent. However, when these TCRs were expressed in CD8- Jurkat cells, the resulting Jurkat cells recognized gp100:209-217 peptide loaded T2 cells and had high functional avidity, but could not recognize HLA-A2+ melanoma cells expressing gp100. Tumor cell recognition by Jurkat cells expressing these TCRs could not be induced by exogenously loading the tumor cells with the native gp100:209-217 peptide. These results indicate that functional avidity of a T cell does not necessarily correlate with TCR affinity and CD8-independent antigen recognition by a T cell does not always mean its TCR will transfer CD8-independence to other effector cells. The implications of these findings are that T cells can modulate their functional avidity independent of the affinity of their TCRs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen Presentation*
  • Antigens, CD / analysis
  • Antigens, Neoplasm / immunology*
  • Cancer Vaccines / immunology*
  • Cancer Vaccines / therapeutic use
  • Cell Line, Tumor / immunology
  • Clone Cells / immunology
  • Clone Cells / metabolism
  • Cytotoxicity, Immunologic
  • Epitopes, T-Lymphocyte / immunology
  • Gene Rearrangement, T-Lymphocyte
  • HLA-A2 Antigen / immunology
  • Humans
  • Immunophenotyping
  • Immunotherapy, Active
  • Jurkat Cells
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Melanoma / blood
  • Melanoma / immunology*
  • Melanoma / therapy
  • Membrane Glycoproteins / immunology*
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Receptors, Antigen, T-Cell, alpha-beta / immunology*
  • Recombinant Fusion Proteins / immunology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocytes, Cytotoxic / immunology*
  • gp100 Melanoma Antigen

Substances

  • Antigens, CD
  • Antigens, Neoplasm
  • Cancer Vaccines
  • Epitopes, T-Lymphocyte
  • HLA-A2 Antigen
  • Membrane Glycoproteins
  • PMEL protein, human
  • Receptors, Antigen, T-Cell, alpha-beta
  • Recombinant Fusion Proteins
  • gp100 Melanoma Antigen