Major histocompatibility complex class II-regulated immunity to murine leukemia virus protects against early T- but not late B-cell lymphomas

Vasmel, W. L. E.; Zijlstra, Maarten; Radaszkiewicz, Thaddäus; Leupers, C. J. M.; Goede, R E de; Melief, Cornelis J.M.

doi:10.1128/jvi.62.9.3156-3166.1988

Cited by 36 publications

(26 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…How retroviruses adapt to the environment encountered in a newly infected host has not been well studied. Immune responses to retroviral envelope proteins are regulated by MHC genes (45)(46)(47). Passage of the Gross MuLV in BALB/c-H-2k mice results in the generation of variant viruses that have lost specific gp70en°epitopes (48) .…”

Section: Resultsmentioning

confidence: 99%

A host gene regulates the structure of the transmembrane envelope protein of murine leukemia viruses.

Coppola

Thomas

1990

The Journal of Experimental Medicine

View full text Add to dashboard Cite

Heterogeneity in the structure of the envelope proteins has been observed in many human and animal retroviruses and may influence pathogenicity. However, the biological significance of this heterogeneity and the mechanisms by which it is generated are poorly understood. We have studied a mouse model in which the envelope gene structure of lymphoma-associated viruses appears to be controlled by a single host gene. The inoculation of HRS and CWD mice with a leukemogenic murine leukemia virus (MuLV) results in recombination between the injected virus and envelope gene sequences of endogenous retroviruses. The genomes of HRS (class I) env recombinants and CWD (class II) env recombinants differ in the sequences encoding the NH2-terminal portion of the transmembrane envelope protein (TM). We have shown that an HRS gene linked to the MHC on chromosome 17 mediates a dominant selection for recombinant retroviruses with the class I envelope gene structure. CBA mice, which share the H-2k haplotype with HRS, also carry the dominant allele at this locus. This system provides a useful model for studies of host factors involved in the selection of specific variants of pathogenic retroviruses.

show abstract

Section: Resultsmentioning

confidence: 99%

A host gene regulates the structure of the transmembrane envelope protein of murine leukemia viruses.

Coppola

Thomas

1990

The Journal of Experimental Medicine

View full text Add to dashboard Cite

show abstract

“…We have been observing homozygous HLA associations in all major leukemias we have studied [1][2][3][4], and are surprised with the lack of attention to "homozygosity" in other genetic studies. The models we started with are the classic mouse leukemia studies, all of which have shown the importance of homozygosity for MHC alleles or haplotypes [22][23][24][25][26]. Heterozygosity for the susceptibility haplotype H-2 k in mouse leukemia and lymphoma does not modify the risk to these malignancies [22][23][24]37].…”

Section: Discussionmentioning

confidence: 99%

“…An ideal study should include as many as possible HLA loci and, whenever possible, selected non-HLA loci. The first truly molecular CML association study by Dorak et al [1] identified several independent markers, as is the case in murine leukemia [22][23][24][25][26]. The main MHC effect on the development of CML is on the age-at-onset as could be predicted from mouse leukemia studies [26].…”

Section: Introductionmentioning

confidence: 99%

“…The first truly molecular CML association study by Dorak et al [1] identified several independent markers, as is the case in murine leukemia [22][23][24][25][26]. The main MHC effect on the development of CML is on the age-at-onset as could be predicted from mouse leukemia studies [26]. The MHCleukemia associations reported to date extend from the hemochromatosis gene [27] to the most centromeric HLA locus -DPB1 in childhood ALL [6].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

HLA system affects the age‐at‐onset in chronic myeloid leukemia

et al. 2003

View full text Add to dashboard Cite

Chronic myeloid leukemia (CML) occurs from childhood to old age. The adult form is characterized by the presence of Philadelphia chromosome resulting from bcr/abl translocation. The BCR-ABL fusion proteins are immunogenic, and the junctional sequences show unique HLA class I and class II restriction patterns in vitro. A previous study in the west of Scotland showed an influence of several HLA genotypes on the age-at-onset of CML. In the present study, we examined the HLA-A, -B, and -DRB1/3/4/5 allele and haplotype distributions in Turkish CML patients diagnosed in a single center where they are routinely HLA-typed by PCR-SSP analysis as a preparation for stem cell transplantation. The patients were 169 subjects of age 17-60 years. The older patients were not HLA typed and missing from the study group. The age-matched control group (n = 213) was healthy blood donors from the same geographical area. HLA-B*37 showed a risk association with CML [P = 0.02; odds ratio (OR) = 5.35]. The DRB1*10 association at similar magnitude was due to its linkage disequilibrium (LD) with B*37. HLA-B*35 and DRB1*11 showed independent protective effects (P = 0.007 and 0.017; OR = 0.54 and 0.60, respectively). The protective association of DRB1*11 may be due to its involvement in the presentation of the common (b3a2) fusion gene. HLA-B*14 and DRB1*01 showed strong LD, and all 5 patients who were positive for the presumed haplotype B*14-DRB1*01 were of age 43 years old or older (P = 0.003), suggesting a delay effect. We also examined the influence of homozygosity for DRB3 (DR52) and DRB4 (DR53) haplotypes on susceptibility. As previously shown in CML and CLL, DRB4 homozygosity was a risk marker (P = 0.01; OR = 3.36), and DRB3 homozygosity was protective (P = 0.007; OR = 0.51). Despite the lack of elderly patients in the study group, the opposite accelerating (DRB4) and delaying (DRB3) effects of homozygous genotypes on the age-at-onset were evident. Besides replicating previously found associations in a different population, this study also suggested new, and probably population-specific associations in CML. The mechanisms by which the HLA system modifies susceptibility to CML are unknown, likely to include immune and nonimmune ones, and worthy of further studies. Am. J. Hematol. 73:256-262, 2003.

show abstract

“…We are interested in the in vivo biological relevance of the proposed selection mechanisms for tumor cells with respect to viral antigen and MHC cell surface expression. We previously described that the H-2 complex strongly influences lymphoma incidence after neonatal infection of C57BL/10 and C57BL/6 mice with mink cell focus-inducing (MCF) MuLV, MCF 1233 virus (25). T cell tumor resistance is dominant, maps to the class II MHC-encoding I-A region, and is associated with high titers ofanti-MuLV antibodies, which develop in the presence ofan adequate I-A-regulated antiviral Th response.…”

mentioning

confidence: 99%

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

Vasmel

Sijts

Leupers

et al. 1989

The Journal of Experimental Medicine

Self Cite

View full text Add to dashboard Cite

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) .

show abstract

Major histocompatibility complex class II-regulated immunity to murine leukemia virus protects against early T- but not late B-cell lymphomas

Cited by 36 publications

References 57 publications

A host gene regulates the structure of the transmembrane envelope protein of murine leukemia viruses.

A host gene regulates the structure of the transmembrane envelope protein of murine leukemia viruses.

HLA system affects the age‐at‐onset in chronic myeloid leukemia

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

Contact Info

Product

Resources

About