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Genetic Control of the Cytotoxic T Cell Response to SV40 Tumor-Associated Specific Antigen¹

From The Wistar Institute of Anatomy and Biology, 36th Street at Spruce, Philadelphia, Pennsylvania 19104

Abstract

The H-2 gene complex controls the ability of mice to generate cytotoxic T cells to the SV40 tumor-associated specific antigen (TASA). Mice of six H-2 haplotypes (H-2^{b, d, f, k, q, and s}) were challenged in vivo with syngeneic simian virus 40 (SV40)-transformed cells. By testing splenic lymphocytes in a ⁵¹Cr cytotoxic test, only H-2^b mice were able to generate cytotoxic T cells specific for syngeneic SV40-transformed target cells. In contrast, immune lymphocytes from both H-2^b and H-2^k mice assayed after secondary in vitro restimulation lysed SV40-transformed target cells of appropriate H-2 genotype. Popliteal lymph node cells from H-2^{b, k, and d} mice, immunized by footpad injection of SV40 and then incubated for 14 days in vitro before assay, are cytotoxic for syngeneic SV40-transformed cells. With this immunization protocol, H-2^b mice respond to SV40 TASA in association with both the H-2 K and D locus-coded molecules, whereas H-2^k mice respond to SV40 TASA in association with the H-2 K molecule only and H-2^d mice respond to SV40 TASA in association with the H-2 D gene product. SV40 TASA-immune lymphocytes from various F₁ (responder x nonresponder) mice were also unable to lyse syngeneic H-2K^d or H-2D^k SV40-transformed target cells. Inhibition of the response to SV40 TASA in association with H-2D^d is found when lymphocytes from SV40 TASA-immune F₁ hybrid (H-2^b x H-2^d) or H-2 congenic recombinant (H-2K^bD^d) mice are analyzed. A dominant suppression or recessive helper mechanism is hypothesized to account for these results.

Footnotes

¹ This work was supported in part by Public Health Service Research Grants CA 18470, CA 20833, and CA 17546 from the National Cancer Institute, and Research Career Award AI 00053 (B. B. K.) from the National Institute of Allergy and Infectious Diseases and by the American Cancer Society (PDT 26, IM-88).

² Present address: Institute for Medical Microbiology, Johannes Gutenberg University, 6500 Mainz, West Germany.

³ Present address: Swiss Institute for Cancer Research, CH 1066 Epalinges, Lausanne, Switzerland.

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