We studied the relative importance of class I and class II major histocompatibility complex (MHC) immunoregulation in the control of Tand B-cell lymphomas induced by murine leukemia virus. Previously, we have described a mink cell focus-inducing (MCF) murine leukemia virus, MCF 1233, which induces not only lymphoblastic T-cell lymphomas but also follicle center cell or lymphoblastic B-cell lymphomas. We now report that the outcome of neonatal infection with MCF 1233 in H-2-congenic C57BL/10 and C57BL/6 mice is decisively influenced by the H-2 I-A locus. A total of 64% of H-2 I-Ak, d mice [B1O.BR, B10.D2, B10.A(2R), B10.A(4R), and B10.MBR] developed T-cell lymphomas after MCF 1233 infection (mean latency, 37 weeks). In contrast, H-2 I-Ab [B10, B10.A(5R), B6], H-2 I_Ab/k [(B10.A x B10)F1 and (BlO x B10.A)F1], and H-2 * Corresponding author.

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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) .