Generation of novel killer hybridomas derived from proliferation-suppressed somatic cell hybrids between YACUT T cell lymphoma and normal lymphocytes activated in secondary mixed lymphocyte cultures.

Somatic cell hybridization between the YACUT T cell lymphoma cell line with normal lymphocytes activated in secondary mixed lymphocyte cultures (MLCs) consistently yielded IL-2-dependent CD4- CD8 alpha+ beta- Fc gamma RIII+ hybrids with cytotoxic function. The hybrids expressed T cell receptors other than that of YACUT origin, and fusion of the YACUT with a CD8 alpha+ beta+ Fc gamma RIII- T cell line also yielded hybrids with an unexpected CD8 alpha+ beta- Fc gamma RIII+ phenotype, which two observations strongly suggested that CD8+ T cells became the parental cell of the hybrids. Prolonged growth of the hybrids with IL-2 resulted in the generation of autonomously growing hybrids (hybridomas) without abrogating the cytotoxic function. The hybridomas exhibited MHC-unrestricted cytotoxicity in a Ca(2+)-dependent manner without prior stimulation and also mediated antibody-dependent cellular cytotoxicity. These results indicate that novel killer hybridomas can be produced following cell transformation of proliferation-suppressed cytotoxic YACUT x MLC cell hybrids. The killer hybridomas may be of value for analyzing recognition mechanisms and molecules involved in MHC-unrestricted cell-mediated cytotoxicity.