Differential expression of major histocompatibility complex class II variants in cells infiltrating the meth A sarcoma.
CD4+ T cells are involved in immune responses against the Meth A sarcoma and infiltrate tumours arising from Meth A cells inoculated intradermally in (BALB/c x C57BL/6)F1 (H-2d/b) mice. In order to investigate whether the prerequisites for tumour antigen presentation to CD4+ T cells are fulfilled within the malignant lesion, expression of class II major histocompatibility complex (MHC) molecules and the costimulatory ligand B7 were examined. The I-Ab and I-Ed allomorphs were abundantly expressed by virtually all B cells and 50% of macrophages infiltrating the tumours. In striking contrast, the I-Ad variant was hardly detectable. This pattern of class II expression appeared to be unique for the tumour microenvironment. Thus the proportion of I-Ad+ spleen B cells and peritoneal macrophages did not significantly differ from the proportion expressing I-Ab and I-Ed, and these extratumoral I-Ad+ cells stained as brightly as did cells from healthy mice. Expression of B7 was weak by tumour-infiltrating cells. The profound capacity of the Meth A sarcoma to confer low local I-Ad and B7 expression might preclude T-cell-dependent anti-tumour immune responses and thus promote survival of malignant cells. Whereas MHC class II genes are generally found to be co-ordinately transcribed, this study demonstrates that the expression of MHC class II allelic variants can be differentially regulated in vivo.
D000818:Animals; D000951:Antigens, Neoplasm; D005260:Female; D015793:HLA-B7 Antigen / Q000096:biosynthesis; D006649:Histocompatibility Antigens; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012513:Sarcoma, Experimental / Q000139:chemically induced / Q000276:immunology*; D014407:Tumor Cells, Cultured