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01-05-2009 | Original Article

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

Authors: 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

Published in: Cancer Immunology, Immunotherapy | Issue 5/2009

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.

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Title: Relationship between CD8-dependent antigen recognition, T cell functional avidity, and tumor cell recognition
Authors: 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
Publication date: 01-05-2009
Publisher: Springer-Verlag
Published in: Cancer Immunology, Immunotherapy / Issue 5/2009
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-008-0594-2

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