Primary virus-induced lymphomas evade T cell immunity by failure to express viral antigens.

Abstract

It is well established that MHC-restricted T cell responses decisively influence the outcome of virus infection (1-3). In the rejection of murine leukemia virus-induced lymphomas, Th and cytotoxic T (Tc) t cells are considered essential effector cells, besides the effects of MuLVspecific antibodies, which can neutralize the virus and inhibit its spread (reviewed in reference 4). Many attempts have been made to characterize the viral antigens that are important in recognition by murine leukemia virus (MuLV)-specific T cells. The presence of viral proteins on the cell surface of MuLV induced tumor cell lines has been documented in a number of serological studies. These cell surface viral proteins, which in processed form are potential target molecules for recognition by Th and Tc cells (5), include the viral env gene-encoded products gPr85env, gp70, and p15(E) and the gag gene-encoded gP95g°g, gP85g°g, p10, pp12, p30, and p15 (reviewed in reference 6). In addition to this, recent data indicate that viral proteins that are not detectable at the surface of cells by serology can also serve as targets for T cells (7). DNA-mediated gene transfer experiments, in which single MuW viral antigens together with particular MHC class I antigens were expressed in heterologous cell lines, and the availability of Tc clones have provided a more subtle analysis of MHC and viral antigen recognition (8, 9). A highly complex picture emerged from these studies, which collectively indicate that both MHC and non-MHC genes determine which viral antigens are recognized in the context of MHC.Recently, substantial progress has been made in the understanding of MHCrestricted recognition ofantigens by T cells. It now appears that T cells usually recognize relatively short antigenic peptides, derived by processing of the native antigen (10, 11). This holds for MHC class II-restricted antigen recognition at the surface of APC by Th cells, but also for MHC class I-restricted antigen recognition by Tc cells, which results in lysis of the antigenic peptide-bearing cells (7,12). The MHCpeptide interaction required for T cell recognition is rather MHC allele specific, which implies that the nature of viral antigens preferentially recognized differs from individual to individual (7,(13)(14)(15)(16)(17) .

Persistent measles virus infection enhances major histocompatibility complex class I expression and immunogenicity of murine neuroblastoma cells

“…molecules. Associative recognition of target cells by CTL depends on the expression of both class I MHC glycoproteins and foreign antigenic determinants on the target cells, therefore it seems reasonable to believe that modulation of either one is a potential mechanism of tumor escape from immune destruction [12,19,20,31,38,40]. Indeed, in acute measles virus infection of neuroblastoma cells, where the expression of H-2K molecules was down-regulated [21], down-regulation of H-2K was inversely correlated with measles virus antigen expression on the cell surface and was associated with decreased susceptibility to lysis by allospecific CTL.…”

Tumor induction by the LTR, v-src, LTR DNA in four B (MHC) congenic lines of chickens

“…RSV tumorigenesis is mediated by the oncogene v-src that, as an integral part of the retroviral genome, can continually spread to neighboring cells by reinfection, which facilitates progression of the tumors (Pontdn 1964). In addition, the products of viral replicative genes, namely env and gag, antigenically modify the infected cells and are responsible for an immune reaction against transformed cells (Poulin et al 1985;Vasmel et al 1989). However, we have demonstrated that only v-src flanked with the long terminal repeats (LTRs) can cause metastasizing tumor in hamsters (Svoboda et al 1983;Geryk et al 1984).…”

Cytotoxic T lymphocytes (CTL) against a transforming gene product select for transformed cells with point mutations within sequences encoding CTL recognition epitopes.

“…Specific CTL recognition of tumor cells requires the presentation by MHC class I molecules of processed tumor antigen to the T lymphocyte antigen receptor. Tumor cell variants that escape CTL immunosurveiUance have been described (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). In most instances, the emergence of CTL escape variant cells is associated with the decrease or absence of MHC class I antigens required for antigen recognition by CTL (11)(12)(13)(14)(15)(16).…”