DEFINITION OF ALIEN H‐2 DETERMINANTS ON A FRIEND LEUKAEMIA BY ANALYSIS OF ALLOREACTIVITY OF CTL FROM PRIMARY MLC

Abstract

A Friend virus-induced tumor of BALB/c (H-2d) [mouse] origin, HFL/d, was examined for the expression of alien H-2 antigens. The alloantigens on HFL/d wer typed by generating CTL [cytotoxic lymphocytes] in primary MLC [mixed lymphocyte culture] with HFL/d as stimulator and measuring reactivity to targets with known H-2 antigens, and confirmed by assessing recognition of HFL/d targets by CTL generated in primary MLC with stimulators expressing known H-2 antigens. Potential cross-reactivities between alloantigens were analyzed by cold-target inhibition experiments. BALB/c cells stimulated with HFL/d lysed H-2b targets, and BALB/c anti-H-2b CTL lysed HFL/d; analysis with recombinant haplotypes demonstrated both H-2Kb and H-2Db alien antigens on HFL/d. C57BL/6 (H-2b) cells stimulated with HFL/d recognized H-2Kd, H-2Dd, and an additional determinant unique to HFL/d. (BALB/c .times. B6)F1 cells also recognized a unique HFL/d determinant not of H-2b or H-2d origin. These unique determinants, which induced a strong cytotoxic response in primary MLC, were not shared by BALB/c or B6 tumors induced by cross-reactive FMR viruses. HFL/d expressed the K and D antigens of its strain of origin, 2 typed alien H-2 antigens, and at least 1 other untyped antigen which may represent an additional H-2 determinant. The studies demonstrate the utility of examining the reactivity of CTL generated in primary MLC to probe for the presence of alien H-2 antigens.