Immunological consequences of T cell- specific expression of H-2Kb molecules in transgenic mice

Key words: major histocompatibility complex, tolerance CBA (H-211) mice carrying a H-2K15 transgene (CD2Kb) linked to transcrlptlonal control elements from the human CD2 gene express H-2Kb at high levels on all thymocytes and peripheral T cells. However, skin grafts from two Independent transgenic lineages, CD2K"-2 and CD2Kb-3, are not rejected by recipient CBA mice. Although mice from both lineages tolerate H-2Kb disparate skin grafts, tolerance is maintained by different mechanisms because H-2Kb-speclfic cytotoxlc T cells cannot be generated In vitro using CD2Kb-2 responder spleen cells, but can be generated when responder cells are from CD2Kb-3 mice. Furthermore, H-2Kb-re8trlcted cytotoxlc T cell responses directed against minor histocompatibility antigens can be obtained from CtWK" ^ responder mice. Thus, negative and positive selection of Immature thymocytes seems to take place In CtWK"^ mice, even though the pattern of H-2K11 expression Is modified by the CD2K " transgene. In contrast, H-2Kb-speclf1c cytotoxlc T cell precursors are not eliminated In CD2Kb-3 mice, even though all thymocytes express H-2K " In these mice. However, these potentially autoreactlve H-2K6-speclflc T cells are apparently Inactive In vivo and fall to lyse syngenelc CD2Kb-3 target cells In vitro, even when activated to lyse other H-2Kb-expres8lng cells. These results reveal that tolerance In CD2Kb-3 mice Is Induced either by a non-deletlonal mechanism or by partial elimination of a subset of cytotoxlc T cell precursors capable of recognizing H-2Kb as a target antigen