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

Tamson V. Moore, Gretchen E. Lyons, Natasha Brasic, Jeffrey J. Roszkowski, Simon Voelkl, Andreas MacKensen, W. Martin Kast, I. Caroline Le Poole, Michael I. Nishimura

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)719-728
Number of pages10
JournalCancer Immunology, Immunotherapy
Volume58
Issue number5
DOIs
StatePublished - May 1 2009

Keywords

  • Affinity
  • Melanoma
  • T cells
  • TCR

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

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