Influence of H-2 antigen expression on killer T cell specificity, differentiation, and induction.

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Abstract
Murine cytotoxic T lymphocytes (CTL) and helper cells are H-2 antigen restricted in their specificity; recognition of foreign antigen by these cells requires the concomitant recognition of self-H-2 molecules. Which H-2 antigens T cells treat as self is determined by the particular H-2 antigens expressed on radioresistant cells of the thymus in which these T cells mature. Using tetraparental [(P1 + P2) .fwdarw. F1] radiation chimeras with in situ F1 thymuses, the H-2 genotype of the stem cells does not influence their H-2 restriction specificity. This allowed the use of tetraparental chimeras that have been thymectomized and grafted with parental (P1, P2, or both) thymus lobes to study the requirements for H-2-restricted T-T interactions during CTL ontogeny and induction. In animals that have received thymus grafts of both parental origins, CTL display no preference for maturation within a syngeneic thymus graft, a finding that is not compatible with a suggested requirement for intrathymic H-2-restricted T-T interactions in the maturation of precursor CTL. Thymectomized tetraparental radiation chimeras were also grafted with thymus grafts from only 1 parent to compare the induction of P1 to P2 CTL in environments in which peripheral (extrathymic) T cell interactions are restricted to 1 H-2 haplotype. No evidence was found for preferential induction of CTL precursors syngeneic to the thymus graft, contrary to expectation if CTL induction requires that T helper cells restricted to thymic H-2 antigens interact directly with precursor CTL. In those animals with 1 parental thymus graft, there is variability in the ratios of P1 and P2 cells induced with several antigens, a finding that may be indicative of an H-2-restricted suppression mechanism operating in the periphery.

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