MEMBRANE ANTIGENS RECOGNIZED BY HETEROANTISERA AGAINST MOUSE TUMOURS,TESTED IN CELL LINES OF DIFFERENT H - 2 HAPLOTYPES

The pattern of reactivity of two heteroantisera against mouse tumour cells (rabbit anti-Meth A sarcoma: RAMA; and rabbit anti-RBL-5 leukaemia: RAR-5) has been studied in various cell lines of different H-2 haplotypes in complement-dependent cytotoxicity tests using a microadioassay. RAMA was cytotoxic not only for Meth A (H-2^d) but also for MCG4, P815Y, LSTRA, YC8 (H-2^d), L929, TLC5, Gardner (H-2^k), RBL-5 and TLX/9 (H-2^b). RAR-5 similarly killed RBL-5, as expected, as well as Meth A, P815Y, MCG4, SL2, YC8, LSTRA (H-2^d), L929 (H-2^k), TLX/9, MBL2, Gil IV, EL4 (H-2^b) and YAC (H-2^a). The cross-cytotoxicity RAMA-RBL-5 and RAR-5-Meth A was abolished when RAMA or RAR-5 were absorbed with allogeneic tissues from C57B1/6, BALB/c, CBA/H, C57B1/10 (B10), B10.BR, B10.D2, but not with rat lymphoid cells. A species-specific antigen present in these strains of mice thus appeared to be responsible for this cytotoxicity. The direct killing obtained with RAMA on Meth A and RAR-5 on RBL-5 was not absorbed by: (a) allogeneic cells of C57B1/6, CBA/H, AKR, B10, B10.BR, B10.D2 for RAMA, and CBA/H, BALB/c, B10, B10.BR, B10.D2 for RAR-5; or (b) syngeneic normal lymphoid cells (BALB/c and C57B1/6 respectively). This suggests the presence of a heteroantibody in the sera recognizing structures at the tumour cell surface that are absent in normal lymphoid cells—a tumour-specific antigen (TSA). Finally, the TSA of Meth A (recognized by BALB/c-absorbed RAMA) did not cross-react with eight mouse cell lines of different aetiology and origin: MCG4, P815Y, Gardner, TLC5, L929, TLX/9, LSTRA and RBL-5. However, the TSA of RBL-5 (recognized by C57B1/6 absorbed RAR-5) reacted not only with RBL-5 but also with tumour cells induced by viruses antigenically related to Rauscher, belonging to the group FMR Gi. It reacted also with EL4, a tumour cell line not virus induced, and weakly with SL2, a spontaneous tumour cell line. It did not react with TLX/9 (X-ray induced) or Meth A (chemically induced). From these results it is concluded that heteroantisera against mouse tumour cells recognize at least species-specific antigens and tumour-specific antigens.