Failure of expression of class I major histocompatibility antigens to alter tumor immunogenicity of a spontaneous murine carcinoma.
We have shown previously that clonal immunogenic variants of murine mammary adenocarcinoma 10.1 can be isolated after treatment in vitro with the DNA-hypomethylating agent 5-azacytidine (5-aza). Such immunogenic variants frequently express elevated class I major histocompatibility complex antigens relative to the level of expression in the parent tumor and are rejected in syngeneic mice by a T-cell-dependent process. To ascertain whether elevated immunogenicity is a function of increased class I antigen expression, we isolated high class I antigen expressors from 5-aza-treated 10.1 cells by using the fluorescence-activated cell sorter. Clonal variants displaying any increase in class I antigen expression were more efficient stimulators of allo-class I antigen-specific cytolytic T-cell precursors. However, these variants displayed unaltered tumorigenicity in immunocompetent syngeneic mice. Thus, phenotypic changes other than, or in addition to, elevated class I antigen expression cause the reduced tumorigenicity of immunogenic clones of 10.1 cells isolated after 5-aza treatment.
Carlow
D A
DA
Department of Neurobiology and Immunology, Mount Sinai Hospital Research Institute, Toronto, ON, Canada.
Kerbel
R S
RS
Elliott
B E
BE
D000230:Adenocarcinoma / Q000276:immunology*; D000818:Animals; D002469:Cell Separation; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D008325:Mammary Neoplasms, Experimental / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D010641:Phenotype; D014407:Tumor Cells, Cultured
D015395:Histocompatibility Antigens Class I