Published in Cancer Detection and Prevention 2000; 24(Supplement 1).

Characterization of tumor antigens involved in the activation of gamma-delta T lymphocytes

E Champagne MD, T Al Saati MD PhD, M Guiraud BS

INSERM U395, Institut Fédératif Claude De Préval, Toulouse, France,

AIMS: Some tumor cell lines are able to activate Vgamma9/Vdelta2 T lymphocytes in vitro. With some tumors (Daudi, Burkitt lymphoma) this process is believed to be T-Cell Receptor (TCR)-mediated and to promote T cell proliferation and effector functions such as proliferation, lymphokine secretion and activation of cytotoxicity, whereas with others such as K562, the process seems TCR-independent and does not promote all effector functions. Our goal is to identify tumor antigens promoting this activation. METHODS: Monoclonal antibodies were produced against the Daudi line, screened for their pattern of reactivity on activatory and non-activatory lines as well as for their modulatory activity on Vgamma9 T cell activation. One antigen, detected with the MAb M5A12D7 was characterized biochemically and morphologically by intracellular facs staining and immunocytochemistry and will be described. RESULTS: We uncovered a tumor antigen present on Daudi and K562 cells which is specifically detected on the surface of HLA-class I deficient tumors although present intracellularly in most haemopoietic lines from which it can immunoprecipitated. It can also be immunoprecipitated from some murine lines and is detected by facs on the surface of the TAP-deficient (and class I) RMA-S murine line. It is thus conserved between man and mouse and plays a part in gamma-delta T cell activation as judged by the modulatory effect of M5A12D7 on the killing of Daudi cells. The antigen is a 55kd, unglycosylated protein. CONCLUSION: M5A12D7 detects a ubiquitous antigen which is selectively detected on the cell surface of HLA-class I deficient tumors and may play a part in gamma-delta T cell activation.

KEY WORDS: Gamma-delta T lymphocytes, tumor antigens, T cell activation, immunosurveillance, innate immunity.

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Paper presented at the International Symposium on Impact of Biotechnology on Cancer Diagnostic & Prognostic Indicators; Geneva, Switzerland; October 28 - 31, 2000; in the section on immunotherapy.