The immunogenicity of experimental tumors is strongly biased by the expression of dominant viral cytotoxic T-lymphocyte epitopes.
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 Vbeta5+ 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.
Iezzi
G
G
Laboratorio di Immunologia dei Tumori, Istituto Scientifico H San Raffaele, Milan, Italy.
Rivolta
L
L
Ronchetti
A
A
Martin-Fontecha
A
A
Rosato
A
A
Protti
M P
MP
Sabbadini
M G
MG
Bellone
M
M
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D005622:Friend murine leukemia virus / Q000276:immunology; D016056:Immunodominant Epitopes / Q000276:immunology*; D007150:Immunohistochemistry; D009052:Leukemia Virus, Murine / Q000276:immunology*; D007942:Leukemia, Experimental / Q000276:immunology; D008223:Lymphoma / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008979:Moloney murine leukemia virus / Q000276:immunology; D009368:Neoplasm Transplantation; D011925:Rauscher Virus / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D013945:Thymoma / Q000276:immunology; D014407:Tumor Cells, Cultured; D014412:Tumor Virus Infections / Q000276:immunology*; D014611:Vaccination / Q000379:methods
D000956:Antigens, Viral; D016056:Immunodominant Epitopes; D016693:Receptors, Antigen, T-Cell, alpha-beta