H-2 heterologous T cell hybridomas were used to study the genetic control of dual, anti-nominal antigen and anti-self H-2 specificity of H-2 restricted T cell factors. Each of four hybridoma clones produced two helper factors. One was restricted for the Ia type of the normal T cell partner (H-2b), whereas the other was restricted for the ia type of the lymphoma partner (H-2k) of the somatic hybrid. This was shown by affinity separation on parental type spleen cells and on monoclonal anti-I-A-Sepharose. Both factors had carrier (chicken gamma globulin; CGG)-specific helper effect, and both bound to anti-VH-315-Sepharose. Because the lymphoma (BW-5147) partner could not contribute a CGG-specific locus, the H-2k-restricted, CGG-specific factor had to be the product of segregating anti-nominal and anti-self loci. This suggests that dual specificity is due to two independent loci and support the validity of dual recognition concepts. Anti-self specificity was associated with homologous Ia alloantigens in the individual factors. Therefore, Ia and anti-self might be linked. Implications of the major histocompatibility complex or VH nature of anti-self receptors and the relationship of T cell factors and receptors was discussed.

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