CD8-independent tumor cell recognition is a property of the T cell receptor and not the T cell.
The CD8 coreceptor enhances T cell function by stabilizing the TCR/peptide/MHC complex and/or increasing T cell avidity via interactions with the intracellular kinases Lck and LAT. We previously reported a CD4(+) T cell (TIL 1383I), which recognizes the tumor-associated Ag tyrosinase in the context of HLA-A2. To determine whether CD8 independent tumor cell recognition is a property of the TCR, we used retroviral transduction to express the TIL 1383I TCR in the CD8(-) murine lymphoma, 58 alpha(-)/beta(-). Immunofluorescent staining of TCR-transduced cells with human TCR V beta subfamily-specific and mouse CD3-specific Abs confirmed surface expression of the transferred TCR and coexpression of mouse CD3. Transduced effector cells secreted significant amounts of IL-2 following Ag presentation by tyrosinase peptide-pulsed T2 cells as well as stimulation with HLA-A2(+) melanoma lines compared with T2 cells alone or HLA-A2(-) melanoma cells. Further analysis of TCR-transduced clones demonstrated a correlation between T cell avidity and cell surface expression of the TCR. Therefore, the TIL 1383I TCR has sufficient affinity to mediate recognition of the physiologic levels of Ag expressed by tumor cells in the absence of CD8 expression.
Roszkowski
Jeffrey J
JJ
Department of Surgery, University of Chicago, Chicago, IL 60637, USA.
Yu
David C
DC
Rubinstein
Mark P
MP
McKee
Mark D
MD
Cole
David J
DJ
Nishimura
Michael I
MI
D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D016827:CD8 Antigens / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D018984:Epitopes, T-Lymphocyte / Q000378:metabolism; D015789:HLA-A2 Antigen / Q000276:immunology / Q000378:metabolism; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism; D008545:Melanoma / Q000235:genetics / Q000276:immunology*; D051379:Mice; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured
D016827:CD8 Antigens; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta