Relationship between CD8-dependent antigen recognition, T cell functional avidity, and tumor cell recognition.
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.
Moore
Tamson V
TV
Department of Surgery, The University of Chicago, Chicago, IL 60637, USA.
Lyons
Gretchen E
GE
Brasic
Natasha
N
Roszkowski
Jeffrey J
JJ
Voelkl
Simon
S
Mackensen
Andreas
A
Kast
W Martin
WM
Le Poole
I Caroline
IC
Nishimura
Michael I
MI
D017951:Antigen Presentation; D015703:Antigens, CD / Q000032:analysis; D000951:Antigens, Neoplasm / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use; D045744:Cell Line, Tumor / Q000276:immunology; D002999:Clone Cells / Q000276:immunology / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015329:Gene Rearrangement, T-Lymphocyte; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D016233:Immunotherapy, Active; D019169:Jurkat Cells; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008545:Melanoma / Q000097:blood / Q000276:immunology* / Q000628:therapy; D008562:Membrane Glycoproteins / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D058951:gp100 Melanoma Antigen
D015703:Antigens, CD; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D008562:Membrane Glycoproteins; C548637:PMEL protein, human; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011993:Recombinant Fusion Proteins; D058951:gp100 Melanoma Antigen