The Journal of Experimental Medicine
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Journal of Experimental Medicine, Vol 150, 51-66, Copyright © 1979 by Rockefeller University Press


ARTICLES

The generation and specificity of cytotoxic T cells raised against syngeneic tumor cells bearing AKR/gross murine leukemia virus antigens

WR Green, RC Nowinski, and CS Henney

Efforts were made to generate C57BL/6 cytotoxic effector cells to a syngeneic leukemia (Emale G2) bearing AKR/Gross virus antigens. As we were unable to induce significant cytotoxic activity by immunization with up to 10(8) irradiated Emale G2 cells, even when cells from such primed animals were subsequently restimulated with Emale G2 cells in vitro, C57BL/6 mice were immunized with an aliogeneic, virus-producing AKR leukemic cell line (AKR SL3).

Peritoneal exudate cells and, to a lesser degree, spleen cells from these mice showed significant lytic activity toward the immunizing allogeneic tumor but not toward Emale G2. When spleen cells were harvested from animals {approximately equal to}10 d after injection of AKR SL3 and rechallenged in vitro with either Emale G2 or AKR.H-2(b) SL1, another tumor that displays AKR/Gross virus antigens, then a vigorous cytotoxic response against Emale G2 and AKR. H-2(b) SL1 was obtained.

Effector cells generated by AKR SL3 priming followed by in vitro stimulation with Emale G2 or AKR.H-2(b) SL1 lysed only cells of H-2(b) haplotype which were strongly positive for the display of serologically detectable AKR/Gross virus antigens. Thus, AKR SL3 cells were not lysed nor were EL4 cells (H-2(b); but only weakly positive for gp70). Cells not bearing the MuLV antigens tested for, such as P815 mastocytoma cells and spleen cell "blasts" from C57BL/6 and CBA (H-2(k)) mice, were also insusceptible to attack. The cytotoxic effector cells induced bore Thy 1.2 alloantigen and were of the Lyt 1+2+ phenotype.

Collectively, these findings are consistent with the conclusion that the cytotoxic T cells raised against Emale G2 are directed against AKR/Gross virus-associated antigens and are H-2 restricted. It will be of interest to determine the relevance of such effector cells to the known resistance of the C57BL/6 mouse to AKR/Gross virus-induced leukemia.
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