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Spontaneous and Induced in Vitro F₁ Anti-Parental Cytotoxic T Lymphocyte Responses: Target Specificities of Cytotoxic Effectors¹

From the Department of Biology, University of California at San Diego, La Jolla, California 92093

Abstract

In vitro cultures of spleen cells from about 5-week-old (AKR/J x BALB/c) or (BALB/c x AKR/J)F₁ mice spontaneously generate CTL that lyse targets from AKR/J, BALB/c, and their F₁ but not allogeneic strains. These spontaneous CTL are not generated in cultures of parental spleen cells and are only detectable in spleen cell cultures from F₁ mice that were heterozygous at both the MHC and background loci.

The same F₁ mice older than 20 weeks of age can respond to parental BALB/c stimulators in an in vitro culture system and generate cytotoxic T lymphocytes (CTL) that lyse BALB/c targets. This response is significantly higher than that seen in unstimulated cultures. The target antigen of these induced F₁ anti-BALB/c CTL maps to H-2D^d but not to H-2K^d, and the CTL lyse not only parental targets but also heterozygous F₁ targets syngeneic to the responder mice. In contrast, anti-H-2K^k CTL induced in the same adult F₁ mice by stimulation with parental AKR/J cells lyse only homozygous H-2K^k targets.

Target antigen mapping as well as cold target competition analyses showed that the target specificities for these spontaneous CTL of the young F₁ mice are indistinguishable from those seen for the induced responses of older mice; i.e., one target maps to K^k, and only homozygous K^k targets are lysed; the other maps to D^d, and homozygous D^d and the F₁ targets are not distinguished.

Footnotes

¹ This work was supported by the National Institutes of Health Grant AI 08795 and the American Cancer Society Grant IM-1K.

² Dr. Ishikawa is supported by Keio University, Tokyo, Japan.