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The Immunogenicity of Experimental Tumors Is Strongly Biased by the Expression of Dominant Viral Cytotoxic T-Lymphocyte Epitopes¹

Laboratorio di Immunologia dei Tumori [G. I., L. R., A. Ron., M. B.], Unità di Immunochimica, Department of Biotechnology [A. M-F.], and School of Medicine, Università degli Studi [M. G. S.], Istituto Scientifico H San Raffaele, Milan 20132, and Istituto di Scienze Oncologiche e Chirurgiche, Università degli Studi, Padova 35128 [A. Ros.], Italy

The immunogenic Friend-Moloney-Rauscher (FMR) virus-induced tumors have been used extensively to clarify the cellular and molecular mechanisms responsible for tumor rejection and to develop immunotherapeutic strategies. We characterize here the trimolecular complex MHC class I-antigenic determinant-T cell receptor involved in the induction of a protective CTL response against the RMA thymoma. This complex is mainly composed by the D^b molecule interacting with a Rauscher virus antigen (Ag) determinant and the Vß5⁺ T cell receptor. We also show that the chemically induced EL-4 thymoma acquires the susceptibility to recognition by anti-RMA CTLs and the ability to elicit a protective anti-RMA CTL response only upon infection by a virus of the FMR family and that RMA and FMR virus infected EL-4 cells share tumor-associated Ag. The data strongly support the hypothesis that the high immunogenicity of virus-induced or infected tumors is determined by the expression of immunodominant virus-encoded Ag. The demonstration of a different outcome in the immune responses elicited in the presence or in the absence of viral Ag further open the contention of the molecular requirements for immunogenicity and should stimulate a more careful revision of unexpected cross-reactivity among tumors.

¹ The work was supported by Associazione Italiana Ricerca sul Cancro and by the Consiglio Nazionale delle Ricerche Applicazioni Cliniche della Ricerca Oncologica.

² To whom requests for reprints should be addressed, at Laboratorio di Immunologia dei Tumori, Istituto Scientifico H San Raffaele, 20132, Milan, Italy. E mail: bellonem@rsisi.hsr.it.

Received 3/ 4/97. Accepted 5/ 9/97.

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