MHC class I antigens and somatic mutants

Abstract

I read with interest the hypothesis offered by T.V. Rajan to explain a possible role for class I major histo- compatibility complex (MHC) anti- gens in the elimination of somatic mutants (Immunol. Today, 1987, 8, 171). I believe, however, that his con- clusions fail to explain the apparently endless number of tumor-specific transplantation antigens (TSTA) or turn- variants of mouse neoplasms ~ . I consider that, even in tumor cells, dass I antigens exist to control abnormal peptides expressed within cells, forming with them an iin- munogenic complex which in turn stimulates T lymphocytes to elimin- ate the cells producing the 'wrong' material. This is supported by the observation that cytosolic proteins may be even more immunogenic l and contain more TSTA determi- L~nants than do cell surface mem- branes 2, a finding which suggests that TSTA 'precursors' originate in the cytoplasm of cancer cells. It is unlikely, however, that more than 100 different molecules (a mini- mum estimate of the number of different TSTAs calculated to exist in a tumor population in the same strain of mice t) can be altered with- out killing the cell. I propose that only a limited number of gene fam- ilies endowed with the ability to generate diversity need be affected by the carcinogen to give rise to hundreds of slightly abnormal pep- tides. In support of this is the fact that the TSTA molecules so far characterized belong to class I-like gene products 3. endogenous retro- viral proteins4, s, immunoglobulin- like prcducts 6, heat-shock proteins 7 and a few others 8. These protein families have in common an ability either to be inserted on the cell surface or to deposit on it, and can thus interact with MHC products. Point-mutated or rearranged pro- ducts of these gene families can thus be transferred as peptides to the cell surface and 'trapped' and trans- formed into TSTAs or turn-variants by class I MHC molecules.