H-2-linked control of resistance to Ectromelia virus infection in 1310 congenic mice

Several B 10 strains of mice, recombinant at theH-2 locus, have been shown to differ in their resistance to infection with ectromelia virus, a natural mouse pathogen. Of 10 strains, 1310, B 10.A(2R), B10.A(4R) and B10.D2 were the most resistant, while B10.G and B 10.A(5R) were the most susceptible. Other strains were intermediate between these extremes. Several genes conferring resistance have been mapped toD ^b in B10.A(2R),K ^k I-A ^k I-B ^k in B10.A,I-J ^b in B10.A(2R) and toD ^d in B 10.T(6R). In general, death among susceptible strains was not a consequence of acute liver necrosis as in other non-B10 strains, and occurred randomly from 8–14 days after infection. The exact cause of death is unknown but is characterized by persisting high titers of virus in the spleen and sometimes the liver, despite an ongoing immune response indicated by strong cytotoxic T-cell activity detectable in the spleens of all mice. The most resistant B10 and B10.A(2R) strains cleared virus from the spleen and liver by 8 days after infection. Analysis of infection in chimeric mice indicates thatH-2 genes, which determine susceptibility to virus persistence in the spleen, operate via radiosensitive cells of the lymphomyeloid system. This evidence, together with several examples ofH-2-linked differences in cytotoxic T-cell responsiveness between resistant and susceptible strains, is consistent with the hypothesis that the mechanism by whichH-2 genes control resistance to ectromelia virus in B10 strain mice is by their influence on the effectiveness of a cell-mediated immune response.     

Accessory cells in the in vitro generation of type C viruses specific T killer lymphocytes. I. Role of macrophages in primary anti-FMR reaction

The role of macrophages has been studied in in vitro cytolytic T lymphocytes- (CTL) mediated responses directed against the FMR cell-surface antigens induced by C type viruses. Macrophages, defined as Thy 1.2-negative, Ia-positive, adherent, phagocytic, radioresistant cells present in the spleen and the peritoneal cavity, are required to obtain primary in vitro anti-FMR responses. In most of our experiments they were not necessary in secondary reactions. In primary responses, macrophages and responder T cells must be compatible at least at the I region of the major histocompatibility complex. Anti-Ia antibodies inhibit the response. A rat soluble factor (Interleukin 2) can replace macrophages in primary anti-FMR CTL-mediated reactions. These results suggest that macrophages function during primary anti-FMR response by interacting with a helper T cell rather than with CTL precursors. In agreement with this hypothesis, it appears that the H-2 restriction of F1 hybrid anti-FMR CTL generated in vitro in primary reaction is not related to the H-2 specificities of the parental macrophages used and depends only on the H-2 antigens of the stimulating tumor cells.     

Experimental allergic orchitis in mice

Inbred strains of mice were studied for their susceptibility to the induction of experimental allergic orchitis after sensitization with mouse testicular homogenate in complete Freund's adjuvant accompanied by injections of extract from Bordetella pertussis. Susceptibility to autoimmune orchitis was found to be linked to the major histocompatibility complex in BALB/c and C57BL/10 mice and mapped to genes encoded within the H-2D ^dregion. In five of six groups of bidirectional (susceptible × resistant) F₁ hybrids, H-2D ^d-linked susceptibility was inherited as a dominant autosomal trait. However, in (BALB/cByJ × DBA/2J)F₁ and (DBA/2J × BALB/cByJ)F₁ hybrids, dominant autosomal resistance to the induction of autoimmune orchitis was observed. Backcross analysis between the resistant F₁ hybrid and the susceptible BALB/cByJ parent suggests that a single independently segregating DBA/2J locus is capable of negating H-2D ^d-linked susceptibility, and controls resistance to the induction of autoimmune orchitis.Abbreviations used in this paper BP extract Bordetella pertussis extract - CFA complete Freund's adjuvant - EAO experimental allergic orchitis - Ir immune response - MHC major histocompatibility complex - MLH mouse liver homogenate - MTH mouse testis homogenate - PI pathology index     

Genetic control of the target structures recognized in hybrid resistance

Hybrid resistance of lethally irradiated (C57BL/6 × DBA/2)F₁ and (C57BL/10 × C3H)F₁ hybrid mice to the engraftment of parental C57BL/6 or C57BL/10 bone marrow cells is controlled by the H-2-linked Hh-1 locus. This resistance can be specifically blocked or inhibited by the injection of irradiated spleen cells from lethally irradiated, marrow reconstituted donor mice of certain strains. By testing the ability of regenerating spleen cells from various donor strains to block the resistance, we studied the genetic requirements for the expression of putative cell-surface structures recognized in hybrid resistance to H-2^b marrow cells. Strains of mice bearing informative intra-H-2 or H-2/ Qa-Tla recombinant haplotypes provided evidence that the Hh-1 locus is located telomeric to the H-2S region complement loci and centromeric to the H-2D region class I locus in the H-2 ^b chromosome. Two mutations that affect the class I H-2D ^b gene have no effect on Hh-1 ^b gene expression. The H-2D region of the H-2 ^S haplotype contains an allele of the Hh-1 locus indistinguishable from that of the H-2D ^b region, as judged by the phenotypes of relevant strains and F₁ hybrids. Collectively these data indicate that the Hh-1 locus is distinct from the class I H-2D (L) locus in the H-2 ^b or H-2 ^s genome, and favor the view that the expression or recognition of the relevant determinants is not associated with class I gene products.Abbreviations used in this paper BM(C) bone marrow (cells) - CML cell-mediated lympholysis - CTL cytotoxic T lymphocytes - FBS fetal bovine serum - HBSS Hanks' balanced salt solution - SC spleen cells from irradiated, bone marrow-reconstituted mice Address correspondence to: Dr. I. Najamura, Department of Pathology, School of Medicine, State University of New York at Buffalo, Buffalo, NY 14214, USA     

H-2-linked genetic control of the plaque-forming cell response to sheep red blood cells

The role of genes linked to the H-2 locus in effecting an immune response to SRBC was examined using strains of mice which differ in the classes of antibodies produced following multiple injections with SRBC. While H-2-linked gene action appeared to be at the level of regulating the number of plaque-forming cells (PFC) present in the spleens of different strains following two injections with SRBC, non-H-2-linked immune response genes seemed to determine whether an IgM-IgG switch occurred as well as how much of each antibody class was produced by the number of PFC available as a result of H-2-linked gene intervention. Mapping studies showed that the H-2-linked genetic effects were due to either the requirement for two genes or the presence of genes located between I-B and H-2D.     

Consequences of a single Ir-gene defect for the pathogenesis of lymphocytic choriomeningitis

The H-2L ^d allele has been identified by others as the sole Ir gene in the H-2 ^d haplotype for the cytotoxic T lymphocyte (CTL) response to mouse lymphocytic choriomeningitis virus (LCMV). The BALB/c-H-2 ^dm2 (C-H-2 ^dm2 ) mutant lacks H-2L ^d , and thus should be ideal for assessing the contribution of virus-immune CTL to LCM immunopathology. Comparison of the C-H-2 dm2 mice with congenic BALB/c mice revealed that there is a delay of about 24 h in the onset of severe inflammatory process and symptoms in the mutant strain, but the absence of H-2L ^d did not prevent the later development of fatal disease in mice injected intracerebrally (i.e.) with neurotropic LCMV. This could indicate that virus-immune CTL are not the major mediators of clinical LCM. Spleen cells from LCMV-primed BALB/c mice did not show CTL activity for LCMV-infected C3H.OH, C-H-2 ^dm2 , or (CBA × C-H-2 ^dm2 )F₁ target cells. However, immune lymphocytes from both the mutant and the F₁ strains lyse virus-infected BALB/c cells. Furthermore, BtO.HTG and, in some experiments, B10.A(5R) mice generated CTL lytic for LCMV-infected BALB/c, C-H-2 ^dm2 , and (CBA × CH-2 ^dm2 )F₁ macrophages. Apparently H-2L ^d is immunodominant in the H-2^d restricted response to LCMV. However, in the absence of H-2L ^d , it seems that H-2K ^d and, to a lesser extent, H-2D ^d also serve as Ir genes for the CTL response in this infection. Even so, the absence of the H-2L^d-restricting element results in a disease process which is either delayed in onset or less severe.     

Immune response to calf collagen type I in mice: A combined control ofIr-1A and nonH-2 linked genes

The genetically controlled immune response to calf skin collagen type I in mice could be demonstrated to be governed by at least two genes. One is linked to theH-2 complex and located within theIA subregion. High-responder alleles areH-2 ^b ,H-2 ^f , andH-2 ^s . The other gene(s) is not linked to theH-2 complex and high-responder allele(s) are found in the genome of B10 mice but not in the genome of DBA mice. There are strong indications that theIr-1A gene controls the response at the T-cell level, whereas it is assumed that the background gene(s) control the immune response at a different level.     

Genetic control of the murine T lymphocyte proliferative response to collagen: analysis of the molecular and cellular contributions to immunogenicity

The genetic control of the murine immune response to denatured beef type II collagen was examined in an antigen-presenting cell-dependent T cell proliferation assay. It was found that the response to collagen is under the control of H-2-linked Ir genes, possibly operating at the level of the antigen-presenting macrophage. Utilizing in vitro cross-stimulation with synthetic collagen-like polypeptides, the data suggest that the antigenic determinants stimulating collagen immune T cells are more dependent on primary amino acid sequence and less on conformation. The implications of such findings for Ir gene specificity and other related immunologic functions is discussed.     

Genetic control of sensitivity to Moloney leukemia virus in mice. II. Mapping of three resistant genes within the H-2 complex.

The level of viremia and the appearance of leukemias were studied after inoculation wtih Moloney leukemia virus (M-MuLV) in different H-2 congenic strains of mice. The viremia was regularly measured on individual mice with a radioimmunoassay of the major internal virion component p30. Three genes within the major histocompatibility complex controlled the level of circulating virus. Two of them, called Rmv.1 and Rmv.2, appear to be located in the I region, respectively, in the IA, and the IC-S or G regions. The third gene, Rmv.3, was mapped to the D end of the complex in the D or T region. Crosses between resistant and sensitive strans demonstrated that the H-2 associated resistance was inherited as a dominant or semi-dominant Mendelian trait. Rmv.1, Rmv.2, and Rmv.3 were shown to complement for resistance in trans when the hybrids between sensitive strains were examined. A good correlation was found between viremia and the appearance of leukemias, the most viremic strains being also the most leukemic. Nevertheless, additional non-H-2 genes must control viremia and/or the appearance of leukemia since, despite high levels of viremia, some sensitive strains do not become leukemic.     

Antitumor effects and immunoregulation mechanisms of IL-23 gene in mouse mammary cancer mediated by retrovirus

Background: Interleukin (IL)-23, composed of p19 and p40 subunits, has diverse functions in regulating immune systems, enhancing cell-mediated immunity. In the present study, we investigated whether forced expression of the p19-linked p40 gene in murine mammary cancer cells (MA891) produced antitumor effects in vivo. Tumor growth of MA-891 cells expressing IL-23 (IL-23/MA891) in mice was retarded compared with parental and vector DNA-transduced tumors and survival of the mice inoculated with IL-23/MA-891 cells was prolonged. Expressions of the CD4⁺ T cells and CD8⁺ T cells were up-regulated not only in IL-23/MA-891 tumor specimens but also in spleen cells of mice inoculated with IL-23/MA-891 as compared with those of mice inoculated with parental or vector DNA-transduced tumors. Cytotoxic CD8⁺ T lymphocyte (CTL) activity of spleen cells from mice inoculated with IL-23/MA-891 was also significantly higher than the other two groups. Th1-type cytokines such as interferon-γ, TNF-α and IL-12p70 secreted from spleen cells of mice bearing IL-23/MA-891 tumors were increased while Th2-type cytokine IL-4 was negative regulated. Moreover, we have identified that the quantity of DC in spleen cells of mice bearing IL-23/MA-891 tumors was increased as compared with those mice bearing parental or vector DNA-transfected tumors.     

Accessory cells in the in vitro generation of type C virus-specific T-killer lymphocytes. III. Two methods of antigen presentation of cytolytic T-lymphocyte precursors

F₁ hybrid mice primed in vivo with tumor cells bearing the virus-induced FMR antigen and the H-2 specificities of each parent are able to produce in vitro in secondary response cytolytic T lymphocytes (CTL) reacting with FMR in the context of the H-2 antigens of both parents. This suggests that the processing in vivo of the immunizing cells by f₁ macrophages results in the presentation of FMR antigens in the context of both H-2 specificities. It has also been suggested that FMR antigens are recognized by cytolytic T-lymphocyte precursors (CTL-P) at the surface of tumor cells and not of macrophages (4). The results reported here show that there are two methods of CTL-P priming: (a) in most cases, FMR antigens are presented directly by the tumor cells; (b) however, in the absence of antigen-presenting tumor cells in vivo or in vitro, macrophages present FMR to CTL-P. The presentation by macrophages appears less efficient but is probably sufficient to explain the priming of memory cells corresponding to both parental H-2.     

Genetic control of immune response to sperm whale myoglobin in mice. I. T lymphocyte proliferative response under H-2-linked Ir gene control.

Studies on the genetic control of immune response to sperm whale myoglobin were initiated. As demonstrated in this paper, the T lymphocyte proliferative response to whale myoglobin is under H-2-linked Ir gene control. Mice of H-2d, H-2f, and H-2s haplotypes were high responders to the myoglobin, whereas haplotypes H-2b, H-2k, H-2p, H-2q, and H-2r were low responders. The Ir gene(s) was localized between H-2K and H2D regions, since the recombinant strain A.TL (KsIkSkDd) was a low responder and A.TH (KsIsSsDd) was a high responder. Further studies with recombinant strains revealed that the expression of the high-responder I-Ad or Ias alleles was sufficient to give a good response, since strains D2.GD (d d b b b b b b) and B10.HTT (s s s s k k k d) were high responders. The expression of the I-Cd allele in strains B10.A (k k k k k d d d) and B10.A(5R) (b b b k k d d d) also gave high response, and thus suggested a second Ir gene, derived from the H-2d haplotype. The finding that expression of the I-Cs allele in B10.S(8R) (k k ? ? s s s s) did not result in high response suggests the lack of the second Ir gene in the high-responder H-2s haplotype.     

Transplantation antigen expression on murine trophoblast detection by induction of specific alloimmunity

Cell-mediated immune responses to murine embryonic trophoblast cells were investigated using lymphocyte trophoblast cultures (LTC) and cell-mediated lympholysis (CML). Spleen cells from CBA (H-2^k) or C57BL/6 (H-2^b) mice hyperimmunized with 3.5-day-old Balb/c (H-2^d) blastocysts did not undergo DNA synthesis after in vitro exposure to Balb/c blastocyst outgrowths nor were cytotoxic lymphocytes (CTL) generated against H-2^d alloantigens. Splenocytes from Balb/c mice presensitized with semiallogeneic (Balb/c female × C57BL/6 male) trophoblast cells derived from 17- to 20-day placental tissue expressed a weak proliferative response in the presence of semiallogeneic placental trophoblast and produced a moderate number of CTL against H-2^b (paternal strain) alloantigens when compared to mixed lymphocyte cultures (MLC) between Balb/c responder and semiallogeneic (stimulator) spleen cells. CTL were also generated in vitro after splenocytes from Balb/c mice hyperimmunized with semiallogeneic spleen cells were restimulated in vitro with placental trophoblast cells. These studies showing that early-stage trophoblast cells fail to evoke transplantation immunity and placental trophoblast is capable of generating alloimmunity only after combined in vivo hyperimmunization with in vitro restimulation suggest that these trophoblast cells are poorly immunogenic due in part to the relatively weak functional expression of major transplantation antigens.     

Suppression of major histocompatibility complex class I and class II gene expression in Listeria monocytogenes-infected murine macrophages

Macrophage cells play a central role during infection with Listeria monocytogenes by both providing a major habitat for bacterial multiplication and presenting bacterial antigens to the immune system. In this study, we investigated the influence of L. monocytogenes infection on the expression of MHC class I and class II genes in two murine macrophage cell lines. Steady-state levels of I-Aβ chain mRNA were decreased in both resting J774A.1 and P388D₁ macrophages infected with L. monocytogenes whereas reduction of H-2K mRNA was only observed in P388D₁ cells. In addition, L. monocytogenes suppressed induction of MHC class I and class II mRNAs in response to γ-interferon as well as the maintenance of the induced state in activated P388D₁ macrophages. Exposure to the non-pathogenic species L. innocua or a deletion mutant of L. monocytogenes, which lacks the lecithinase operon, did not cause a reduction in H-2K and I-Aβ mRNA levels nor suppress expression of Ia antigens. Inhibition of MHC gene expression may represent an important part of the cross-talk between L. monocytogenes and the macrophage that probably influences the efficiency of a T cell-mediated immune response and thus the outcome of a listerial infection.     

Immune responses to complex protein antigens I. MHC control of immune responses to bovine albumin

Murine T cell proliferative and antibody responses to the multi-determinant protein bovine serum albumin (BSA) are controlled by Ir genes mapping within the H-2 gene complex. Strains possessing the H-2k, H-2a, and H-2d haplotypes are classified as high responders to BSA. In contrast, H-2b strains are low responders to BSA. Genetic mapping experiments employing strains with recombinant H-2 haplotypes indicate that both T cell proliferative and antibody responses are at least in part regulated by genes within the I-A subregion. Studies on the inhibition of T cell proliferation by monoclonal anti-Ia antibodies are consistent with the assignment of an Ir gene for BSA to the I-A subregion and strongly suggest a role for genes within the I-E/C subregions as well. The MHC-mediated control of antibody responses did not affect the affinity or the isotype of the antibody produced. The relative quantities of antibody specific for each of the three domains of BSA appears to be regulated by H-2-linked BSA Ir genes, and domain III antigenic determinants were found to be dominant in the responses of low-responder mice and in the early response of high-responder mice. This domain III epitope dominance essentially disappears by the tertiary response of high-responder mice.     

A third class I major histocompatibility complex antigen encoded by a gene in the D region of the H-2 d haplotype recognized by cytotoxic T lymphocytes

The D region of the H-2 ^d haplotype contains five class I genes: H-2D ^d , D2 ^d , D3 ^d , D4 ^d and H-2L ^d . Although previous studies have suggested the presence of D-end encoded class I molecules in addition to H-2D^d and H-2L^d, segregation of genes encoding such molecules has not been demonstrated. In this report we have used cãtotoxic T lymphocytes (CTL) to examine the D region of the H-2 ^d haplotype for the presence of additional class I molecules. CTL generated in (C3H × B6.K1)F₁ (K ^k D ^k , K ^b D ^b ) mice against the hybrid class I gene product Q10^d/L^d expressed on L cells cross-react with H-2L^d but not H-2D^d molecules, as determined by lysis of transfected cells expressing H-2L^d but not H-2D^d. Although H-2L^d-specific monoclonal antibodies (mAb) completely inhibit H-2L^d-specific CTL from killing B10.A(3R) (K ^b D ^d L ^d ) target cells, only partial inhibition of anti-Q10 CTL-mediated lysis was observed, suggesting the presence of an additional D-end molecule as a target for these latter CTL. To identify the region containing the gene encoding the Q10 cross-reactive molecule, we show that anti-Q10 CTL lyse target cells from a D-region recombinant strain B10.RQDB, which has H-2D ^d , D2 ^d , D3 ^d , D4 ^d , and H-2D ^b but not the H-2L ^d H-2 ^d , and H-2L ^d (including D2 ^d , D3 ^d , and D4 ^d , lacks this anti-Q10 CTL target molecule. Together, these data demonstrate that a class I gene mapping between H-2D ^d and H-2L ^d encodes an antigen recognozed by anti-Q10 CTL. A likely candidate for this gene is D2 ^d , D3 ^d or D4 ^d .     

H-2-linked Ir gene control of T cell recognition of the Sm nuclear autoantigen and the aberrant response of autoimmune MRL/Mp-+/+ mice

We have examined T cell recognition of the nuclear autoantigen Sm. Rabbit Sm-primed cells from autoimmune MRL/Mp-+/+ (+/+) mice and from all normal strains tested were able to proliferate to rabbit Sm in vitro. In contrast, the reactivity of normal strains to Sm of murine origin was genetically restricted; only H-2f strains B10.M and A.CA, and H-2s strains B10.S and A.SW could recognize mouse Sm, suggesting that responsiveness to mouse Sm was under the control of H-2-linked Ir genes. Although five Iak-bearing normal strains (B10.A, B10.A(2R), B10.BR, A/Sn, and CBA) did not recognize mouse Sm, autoimmune +/+ (Iak) mice were responders. The responsiveness of the +/+ mice to Sm was probably not due to differences in their Iak region, compared with other strains, because the Iak region of normal strains and the autoimmune +/+ strain were indistinguishable by interstrain MLC, immune response gene product function, and recognition by anti-Iak mAb. Inhibition of Sm-induced proliferation by mAb demonstrated that T cells from autoimmune +/+ mice, responder normal strains, and nonresponder normal strains recognized rabbit and mouse Sm in the context of I region-encoded products. The T cell response to Sm antigen in normal mice is therefore Ia region restricted and, for the murine antigen, under Ir gene control. Autoimmune mice that spontaneously make anti-Sm antibodies (+/+) also perceive Sm in an Ia-restricted manner, but their responder status abrogates H-2-linked Ir gene control.     

Nonequivalence of Classical MHC Class I Loci in Ability to Direct Effective Antiviral Immunity

Structural diversity in the peptide binding sites of the redundant classical MHC antigen presenting molecules is strongly selected in humans and mice. Although the encoded antigen presenting molecules overlap in antigen presenting function, differences in polymorphism at the MHC I A, B and C loci in humans and higher primates indicate these loci are not functionally equivalent. The structural basis of these differences is not known. We hypothesize that classical class I loci differ in their ability to direct effective immunity against intracellular pathogens. Using a picornavirus infection model and chimeric H-2 transgenes, we examined locus specific functional determinants distinguishing the ability of class I sister genes to direct effective anti viral immunity. Whereas, parental FVB and transgenic FVB mice expressing the H-2K^b gene are highly susceptible to persisting Theiler''s virus infection within the CNS and subsequent demyelination, mice expressing the D^b transgene clear the virus and are protected from demyelination. Remarkably, animals expressing a chimeric transgene, comprised primarily of K^b but encoding the peptide binding domain of D^b, develop a robust anti viral CTL response yet fail to clear virus and develop significant demyelination. Differences in expression of the chimeric K^bα1α2D^b gene (low) and D^b (high) in the CNS of infected mice mirror expression levels of their endogenous H-2^q counterparts in FVB mice. These findings demonstrate that locus specific elements other than those specifying peptide binding and T cell receptor interaction can determine ability to clear virus infection. This finding provides a basis for understanding locus-specific differences in MHC polymorphism, characterized best in human populations.     

H-2 linked Ir gene control of antibody responses to porcine insulin. I. Development of insulin-specific antibodies in some but not all nonresponder strains injected with proinsulin

Cell-mediated and humoral immune responses to heterologous insulins in mice are controlled by H-2 linked, dominant, immune response (Ir) genes. For example, mice bearing the H-2d haplotype develop T cell proliferative responses and produce antibody after injection with porcine insulin, whereas mice bearing other H-2 haplotypes do not. Data presented in this communication demonstrate that homozygous and heterozygous H-2d mice produce insulin-binding antibodies when immunized with porcine insulin or proinsulin. Some (H-2b,k,s) insulin-nonresponder mice produce insulin-binding antibodies after injection of proinsulin, whereas other insulin-nonresponder strains (H-2q) do not. All strains, except homozygous H-2q mice, produce antibodies specific for proinsulin, suggesting that the response to porcine proinsulin is also controlled by H-2-linked Ir genes. More importantly, F1 hybrids between insulin-nonresponder C57BL/10 (H-2b) and DBA/1 (H-2q) produce no insulin-binding antibodies when injected with proinsulin, despite the fact that proinsulin-binding antibodies are produced by these mice.     

Variation of expression of histocompatibility antigens on tumor cells: absence of H-2Kk-gene products from a gross-virus-induced leukemia in BALB.K

The antigenic profile of the K-GV tumor of BALB.K origin, induced by Gross virus and maintained in vitro and in vivo, was investigated by serological and immunochemical methods and techniques of cell-mediated immunity. The H-2K^k-gene products were absent by several criteria: (1) monoclonal antibody and conventional alloantisera directed against the H-2K^k antigenic specificities were nonreactive by direct testing and by absorptions. (2) H-2K^k products could not be precipitated from glycoprotein or protein extracts of the radiolabeled K-GV tumor. (3) Cytotoxic effectors against H-2K^k produced by sensitization in vitro and in vivo failed to kill K-GV target cells. (4) The tumor could neither stimulate BALB.B congenic mice to produce cytotoxic effectors nor specific cytotoxic antibody against H-2K^k-gene products. In contrast, the H-2D^k antigen was readily detectable by all these criteria. These findings therefore describe a tumor which has selectively lost the H-2K-gene products. The K-GV tumor was able to generate Gross-virus-specific CTL, but had greatly reduced susceptibility to lysis by Gross-virus-specific CTL generated by H-2K expressing AKR (H-2 ^k) tumors. These findings have important implications for the associative recognition of tumor antigens and the immune surveillance of virally induced tumors.Abbreviations used in this paper MHS major histocompatibility system - LcH Lens culinaris hemagglutinin - SDS sodium dodecyl sulfate - CTL cytotoxic T lymphocytes - GCSA Gross-virus-induced cell-surface antigen - MuLV murine leukemia virus