G. Iezzi et al., THE IMMUNOGENICITY OF EXPERIMENTAL-TUMORS IS STRONGLY BIASED BY THE EXPRESSION OF DOMINANT VIRAL CYTOTOXIC T-LYMPHOCYTE EPITOPES, Cancer research, 57(13), 1997, pp. 2564-2568
The immunogenic Friend-Moloney-Rauscher (FMR) virus-induced tumors hav
e been used extensively to clarify the cellular and molecular mechanis
ms responsible for tumor rejection and to develop immunotherapeutic st
rategies. We characterize here the trimolecular complex MHC class I-an
tigenic determinant-T cell receptor involved in the induction of a pro
tective CTL response against the RMA thymoma. This complex is mainly c
omposed by the D-b molecule interacting with a Rauscher virus antigen
(Ag) determinant and the V beta 5(+) T cell receptor. We also show tha
t the chemically induced EL-4 thymoma acquires the susceptibility to r
ecognition by anti-RMA CTLs and the ability to elicit a protective ant
i-RMA CTL response only upon infection by a virus of the FMR family an
d that RMA and FMR virus infected EL-4 cells share tumor-associated Ag
. The data strongly support the hypothesis that the high immunogenicit
y of virus-induced or infected tumors is determined by the expression
of immunodominant virus-encoded Ag. The demonstration of a different o
utcome in the immune responses elicited in the presence or in the abse
nce of viral Ag further open the contention of the molecular requireme
nts for immunogenicity and should stimulate a more careful revision of
unexpected cross-reactivity among tumors.