Alloantisera Reacting With Tumor Cells of Inappropriate Haplotype. I. Characterization of Target Antigens

Unexpected complement-dependent cytotoxic reactions of some mouse alloantisera produced against H-2 specificities, which according to the H-2 chart are expressed only by H-2^dand H-2^bhaplotypes, were detected against a 7, 12-dimethyl- benz[a]anthracene-induced leukemia in SJL/J mice (H-2^shaplotype). Antibodies directed against H-2 specificities were thought to be responsible for such reactivities on the basis of the following observations: a) Absorption of the alloantisera with normal lymphoid cells from mice expressing the appropriate haplotypes (B10.D2-H-2^dand C57BL/6-H-2^b) specifically removed all the cytotoxicity against the leukemia cells; b) soluble H-2 molecules purified about 200-fold from spleens of A/J, BALB/c, or C57BL/6 mice fully inhibited the cytotoxic reactivities of the appropriate antisera. These cross-reacting specificities did not seem to be C-type viral structural antigens and were not tumor- specific, inasmuch as they were also expressed by two other leukemias induced by the same chemical carcinogen in the same mouse strain. Normal cells from SJL/J mice, although not a target in the direct cytotoxicity assay, were able to completely absorb the reactivity of the alloantisera against the tumor cells and therefore also expressed the antigens. The results suggest that previously undetected public specificities on H-2 molecules were reacting with these antisera and that neoplastic transformation could alter them so that they became cytotoxic targets on tumor cells.