The role of MHC class I glycoproteins in the regulation of induction of cell death in immunocytes by malignant melanoma cells

A deranged expression of MHC class I glycoproteins, characteristic of a var iety of malignancies, contributes to the ability of cancer to avoid destruc tion by T cell-mediated immunity. An abrogation of the metastatic capacity of B16 melanoma cells has been achieved by transfecting an MHC class I-enco ding vector into class I-deficient B16 melanoma clones [Gorelik, E., Kim, M ., Duty, L. & Calili, U. (1993) Clin. Exp. Metastasis 11, 439-452]. We repo rt here that the deranged expression of class I molecules by B16 melanoma c ells is more than a mere acquisition of the capacity to escape immune recog nition. Namely, cells of the B16 melanoma prompted splenic lymphocytes to c ommit death after coculture, However, a class I-expressing and nonmetastati c CL8-2 clone was found to be less potent as an inducer of apoptosis than c lass I-deficient and metastatic BL9 and BL12 clones. Both Thy1.2(+) and Thy 1,2(-) splenocytes underwent cell death when exposed to the class I-deficie nt BL9 clone. A proportion of CD4(+) and CD8(+) cells among splenocytes exp osed to the BL9 clone was lower than that observed in a coculture with cell s of the CL8-2 clone. Consistently, none of the melanoma clones studied pro duced a ligand to the FAS receptor (FAS-L). Thus, our results provide evide nce that (i) the production of FAS-L may not be the sole mechanism by which malignant cells induce apoptosis in immunocytes, and (ii) absence of MHC c lass I glycoproteins plays an important role in preventing the elimination of potential effector immunocytes by tumor cells.