THE KILLING OF TUMOR-CELL TARGETS COUPLED TO TUBERCULIN (PPD) BY HUMAN AND MURINE PPD-REACTIVE T-HELPER CLONES .2. MAJOR HISTOCOMPATIBILITY COMPLEX RESTRICTION OF KILLING

This paper takes up the major histocompatibility complex (MHC) restriction of killing by a murine and a human tuberculin (PPD)-specific T helper clone of PPD-Con A bound targets. In the previous paper we demonstrated that the specificity of killing of such targets was directed against PPD and not the lectin. This paper provides further evidence to suggest that the PPD-specific clones recognize PPD on PPD-Con A-bound cells through the T cell antigen receptor complex, since the killing was restricted by MHC class II products. Using a range of syngeneic, allogeneic, and semi-syngeneic targets we have shown the fine specificity of the restricting element to be one of the two alleles of the DR region (DR2) for the human clone, and to be the I-A subregion for the murine clone. Binding sites with radiolabelled class II antibodies were performed to see whether killing efficiency was dependent on the number of class II products expressed. The findings showed that the human B-EBV targets express 2-3 .times. 106 molecules per cell, while the susceptible murine tumours, the Abelson line and the 6A tumour, only expressed 600-800 binding sites per cell. Target cell susceptibility appeared to be linked to the number of class II molecules expressed; thus the syngeneic murine MBL-2 tumour expressing 200-300 binding sites per cell was not killed and the lysis of the 6A and Abelson tumours could be enhanced by doubling the number of class II binding sites by incubating cells with Con A-conditioned medium. However, maximum lysis did not exceed 30-40%, suggesting that class II expression alone did not govern killing.