Lack of class I H-2 antigens in cells transformed by radiation leukemia virus is associated with methylation and rearrangement of H-2 DNA.

Meruelo, Daniel; Kornreich, Ruth; Rossomando, Anthony; Pampeno, Christine; Boral, Aparna; Silver, J; Buxbaum, Joel N.; Weiß, Elisabeth H.; Devlin, James J.; Mellor, Andrew L.

doi:10.1073/pnas.83.12.4504

Cited by 37 publications

(17 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Data have been obtained on the murine GR9 tumour which substantiate different class I methylation patterns between class I positive and negative tumour clones (Bonal et al, 1986). The loss of H-2 molecules in SV-40 and radiation leukaemia virus induced tumours is associated with H-2 class I gene rearrangement or CCGG hypermethylation (Rogers et al, 1983, Meruelo et al, 1986. Loss of HLA class I gene restriction fragments has been described in human melanoma (Angelini et al, 1986) and colorectal carcinoma (Bar-Eli et al, 1987).…”

Section: Discussionmentioning

confidence: 99%

HLA class I gene expression on human primary tumours and autologous metastases: demonstration of selective losses of HLA antigens on colorectal, gastric and laryngeal carcinomas

Esteban²,

Ferrón³

et al. 1989

Br J Cancer

118

View full text Add to dashboard Cite

Summary The expression of HLA class I antigens was studied in 99 primary tumours (colorectal, gastric and laryngeal carcinomas) and 57 autologous metastases using immunohistological techniques and monoclonal antibodies against class I monomorphic determinants, HLA-B isotypic determinants and HLA polymorphic determinants. Fourteen per cent of colorectal, 9.6% of gastric and 20% of laryngeal carcinomas completely lacked class I molecules. Selective losses of HLA-B antigens were also detected in 8.8, 3.4 and 5.8% of these tumours respectively. Taking into account complete and selective loss of HLA-B the average alteration in the class I molecules expression totalled 21%. The comparison of class I expression between primary tumours and autologous metastases showed differences in 24% of the patients. These differences consisted mainly in a decrease of class I expression by metastases. Nevertheless, four types of divergence were detected in laryngeal carcinomas, namely: + / -, + / +, -/ +, -/-. In addition, a clear correlation between degree of differentiation and class I expression was observed in laryngeal tumours. Finally, when class I gene RFLPs were compared with DNA from 15 tumours and autologous normal mucosa or peripheral lymphocytes, no differences were detected between these samples.

show abstract

Section: Discussionmentioning

confidence: 99%

HLA class I gene expression on human primary tumours and autologous metastases: demonstration of selective losses of HLA antigens on colorectal, gastric and laryngeal carcinomas

Esteban²,

Ferrón³

et al. 1989

Br J Cancer

118

View full text Add to dashboard Cite

show abstract

“…In their study of radiation leukemia virus (RadLV), another MuLV that modifies H-2 expression, Merulo et al (31) obtained evidence for altered methylation and structural rearrangements of the H-2 complex in RadLV-induced tumors, presumably because of integration of viral genomes. Like M-MuLV, RadLV enhances H-2 expression in cells soon after infection (6,32 Fig.…”

Section: Downloaded Frommentioning

confidence: 99%

Murine retroviruses control class I major histocompatibility antigen gene expression via a trans effect at the transcriptional level.

Wilson¹,

Flyer²,

Faller³

1987

Mol. Cell. Biol.

View full text Add to dashboard Cite

Moloney murine leukemia virus (M-MuLV) and Moloney murine sarcoma virus (M-MSV) exert a regulatory effect on the class I genes of the murine major histocompatibility complex (MHC). We have previously shown that M-MuLV infection of mouse fibroblasts results in a substantial increase in cell surface expression of H-2K, H-2D, and H-2L proteins, whereas M-MSV, upon coinfection of the same cells, is apparently able to override the MuLV-induced increase in H-2 expression. As a result of this modulation, immune recognition of the infected cells is profoundly altered. Our efforts have been directed toward elucidating the molecular basis for this phenomenon. We report here that stimulation of interferon production as a result of infection with MuLV does not occur and, therefore, is not the cause of MuLV-induced enhancement of MHC expression. Control of H-2 class I and 02-microglobulin gene expression by M-MuLV, and probably by M-MSV, takes place at the transcriptional level as indicated by nuclear runoff studies and analysis of steady-state mRNA levels. Our demonstration that M-MuLV controls expression of widely separated endogenous cellular genes (those coding for H-2D, H-2K, H-2L, and (l2-microglobulin), transfected class I MHC genes, and unintegrated chimeric genes consisting of fragments of class I MHC genes linked to sequences encoding a procaryotic enzyme, chloramphenicol acetyltransferase, suggests that M-MuLV exerts its effect in trans and not by proviral integration in the vicinity of the H-2 gene complex. Finally, we show that the sequences of at least one MHC gene, which are responsive to trans regulation by M-MuLV, lie within 1.2 kilobases upstream of the initiation codon for that gene. Class I genes of the H-2 gene complex in mouse, and the HLA complex in humans, encode protein products which are expressed in association with P2-microglobulin on the surfaces of nucleated cells (23). In addition to serving as the target molecules in allogeneic graft rejection, these proteins are essential for the recognition and elimination of neoplastic and virus-infected cells by the cytotoxic T cells (CTLs) of the host immune system (37, 44). The level of expression of H-2 class I proteins on virus-infected cells has been correlated with the degree of effectiveness with which they are destroyed by the CTLs (18, 34). It is, therefore, reasonable to expect that viruses with the capability of altering H-2 expression in the cells they infect may be influencing their own survival.Previously, this laboratory has reported that cells chronically express significantly increased surface levels of H-2K, H-2D, and H-2L proteins after infection with the Moloney murine leukemia virus (M-MuLV) (18). These infected cells are efficiently lysed by M-MuLV-specific CTLs and also by allospecific CTLs, a reflection of their increased level of H-2 class I antigens. Coinfection of cells with M-MuLV and the replication-defective, acutely transforming Moloney murine sarcoma virus (M-MSV) eliminates the H-2 enhancement, as well as profoundly decreas...

show abstract

“…They include tumors induced by DNA viruses (15,23,28), RNA viruses (7,17,22), and chemical carcinogens (5). The observed suppression may have arisen either directly by the expression of specific gene products (1)(2)(3)27) or indirectly through mechanisms involving immunoselection (9,20).…”

mentioning

confidence: 99%

Rejection of B16 melanoma induced by expression of a transfected major histocompatibility complex class I gene.

Tanaka¹,

Gorelik²,

Watanabe³

et al. 1988

Mol. Cell. Biol.

View full text Add to dashboard Cite

Transfection of a functional major histocompatibility complex class I gene into certain tumor cells, induced by oncogenic viruses or chemical carcinogens, can effectively abrogate their tumorigenic activity. Since experimentally induced tumors possess strong tumor-specific transplantation antigens, expression of cell surface class I antigens may present the tumor cells to appropriate immune effector cells. Most spontaneously arising tumors do not possess tumor-specific transplantation antigens, and their tumorigenicity may not be affected by the expression of a transfected class I gene. We demonstrate that the poorly immunogenic B16-BL6 melanoma can be rendered nontumorigenic in syngeneic mice by the expression of the class I H-2K antigen but not the class II I-A antigen. Furthermore, the poorly tumorigenic, class I-expressing B16-BL6-transfected cells can effectively immunize syngeneic C57BL/6 mice against the highly tumorigenic, class I-deficient B16-BL6 parental cells. Our success in experimentally manipulating the tumorigenicity of a spontaneously derived neoplasm offers hope for a potential modality for the effective treatment of human cancer.

show abstract

Lack of class I H-2 antigens in cells transformed by radiation leukemia virus is associated with methylation and rearrangement of H-2 DNA.

Cited by 37 publications

References 17 publications

HLA class I gene expression on human primary tumours and autologous metastases: demonstration of selective losses of HLA antigens on colorectal, gastric and laryngeal carcinomas

HLA class I gene expression on human primary tumours and autologous metastases: demonstration of selective losses of HLA antigens on colorectal, gastric and laryngeal carcinomas

Murine retroviruses control class I major histocompatibility antigen gene expression via a trans effect at the transcriptional level.

Rejection of B16 melanoma induced by expression of a transfected major histocompatibility complex class I gene.

Contact Info

Product

Resources

About