Expression of hybrid Ia molecules on the cell surface of reticulum cell sarcomas that are undetectable on host SJL/J lymphocytes.

SJL/J (H-2 (8)) lymphocytes, primed in vitro against primary, cultured, and transplantable syngeneic reticulum cell sarcomas (RCS) were found to recognize and bind to the tumor without subsequent cytolysis. Additional data showed that the recognition was also directed against Ia molecules of the H-2(d), but not H-2(k), haplotype. Normal spleen cells of DBA/2, B 10.D2, and B 10.OL mice were bound, whereas those of CBA, B 10.BR, B 10.A, B 10.GD, and D2.GD were not. Furthermore, the Ia molecules were in the form of a hybrid, because spleen cells from F(1) progeny of a B10.A and a B10.GD parent were recognized and bound as effectively as the RCS. Recognition was not restricted solely to the H-2(d) haplotype. Spleen cells from B10.S(9R) mice were also significantly bound. This result suggested that the RCS expresses a hybrid Ia molecule containing a beta-chain of the H-2(8) haplotype. Recognition of this hybrid Ia molecule by the host resulted in a cross- reactive recognition of H-2(d) specificities. Further analysis revealed that the RCS express on their cell surface an alpha-chain of the hybrid Ia molecule which is involved in host anti-tumor recognition. Preincubation of the RCS with monoclonal antibody directed against the Ia.7 specificity on the alpha-chain could block lymphocyte-to-tumor cell binding. The blocking activity could be removed by preabsorption of the antibody on the RCS, as well as normal Ia.7-bearing lymphocytes, but not on lymphocytes that do not express Ia.7, such as SJL/J. The data suggest that the hybrid Ia molecules expressed on the RCS, and recognized by tumor-primed syngeneic lymphocytes, are composed of both a syngeneic and an alien chain. The component alien to the SJL/J host is the Ia.7-bearing alpha-chain. Normal SJL/J cells synthesize but do not express the beta-chain. In the RCS, however, alien alpha-chain synthesis permits expression of the syngeneic beta-chain in the form of a hybrid Ia molecule.