Molecular aberrations in the MHC class I-restricted pathway for antigen presentation in methylcholanthrene sarcomas from nude mice: discrepancies between MHC mRNA and surface protein.
In a previous study, we demonstrated that eight sarcomas induced by chemical carcinogenesis in nude mice were rejected by syngeneic immunocompetent recipients at a much higher rate than eight sarcomas induced with the same method in syngeneic immmunocompetent mice. In the present study, we investigated these 16 sarcomas for structural and quantitative aberrations in components of the MHC class I-restricted antigen-processing and -presentation pathway. Considerable discrepancies between mRNA levels and cell surface protein expression of MHC class I (Kd, Dd and Ld) molecules were observed almost exclusively in the tumours derived from nude mice. Several of the nude mouse-derived tumours also displayed incongruent levels of heavy chain mRNA and beta2-microglobulin mRNA. These findings are taken as indications of abnormal regulation of gene transcription in nude mouse tumours, and if this abnormal regulation extends to the entire genome, it may explain the pronounced immunogenicity of these tumours. Proteasome composition, heat shock protein expression, TAP-molecule inducibility and intercellular adhesion molecule-1 expression were investigated in the same tumours. We found no indications of structural defects or quantitative differences in these molecules between the two groups of tumours.
Engel
A M
AM
Institute for Medical Microbiology and Immunology, University of Copenhagen, Panum Institute, Denmark.
Svane
I M
IM
Madsen
M W
MW
Pedersen
M
M
Werdelin
O
O
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology*; D015152:Blotting, Northern; D015342:DNA Probes / Q000737:chemistry; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005805:Genes, MHC Class I / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008748:Methylcholanthrene; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D012333:RNA, Messenger / Q000032:analysis; D012513:Sarcoma, Experimental / Q000139:chemically induced / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D001613:beta 2-Microglobulin / Q000276:immunology
D000951:Antigens, Neoplasm; D015342:DNA Probes; D015395:Histocompatibility Antigens Class I; D012333:RNA, Messenger; D001613:beta 2-Microglobulin; D018799:Intercellular Adhesion Molecule-1; D008748:Methylcholanthrene