Cytotoxic Antibodies in the Homograft Reaction

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Abstract
An analysis was made of the cytotoxic isoantibodies that can be demonstrated in vitro by the addition of complement, using, mainly, the strain specific tumors 6C3HED and DBA, and the homotransplantable MC1M, MC1A, 6C3HED-ICR and DBA-ICR. Homografts of the strain-specific tumors can elicit production of the cytotoxic antibodies. The cytotoxins produced by 6C3HED are effective against 6C3HED but not against MC1M, though homografts of MC1M and of normal C3H tissues can elicit cytotoxins active against both MC1M and 6C3HED. Cells of 6C3HED therefore possess one toxinogen, C′, shared by MC1M and normal C3H tissues, whereas the latter possess a second toxinogen, M′, which is not present in 6C3HED. This was confirmed by absorptive experiments. Homografts of MC1A, 6C3HED-ICR, and DBA-ICR, did not elicit production of the cytotoxic antibodies. These tumors were also not affected by the cytotoxins produced by 6C3HED, MC1M, or DBA. DBA-ICR lost the toxinogens of DBA. Cells of MC1A and 6C3HED-ICR lost the C′ antigen of 6C3HED and the M′ of MC1M. In vitro absorption tests demonstrated that MC1A possesses a nontoxinogenic antigen, A′, that is related to an MC1M toxinogen. MC1M has the antigenic constitution, C′, M′, A′, with C′ and A′ forming a complex antigen that produces a complex antibody molecule. It was shown that in the absence of added complement, these cytotoxic antibodies do not produce a destruction of the tumor cells in vivo. Thus they seem to play no direct role in the homograft reaction.