Tolerance and MHC restriction in transgenic mice expressing a MHC class I gene in erythroid cells

Transgenic mice carrying a MHC class I structural gene (H-2K^b) linked to transcriptional control elements from the human β-globln gene, which direct erythroid lineage specific transcription, express H-2K^b molecules In red blood cells but H-2K^b expression cannot be detected in skin or lymphoid cells. This limited pattern of self MHC expression is sufficient to Induce tolerance to H-2K^b molecules and H-2K^b restricted cytotoxic T cell responses can be generated in transgenic mice. Transgenic mice are unable to mount H-2K^b specific cytotoxic T cell responses in vitro, even when exogenous IL-2 is provided. However, H-2K^b specific T cell proliferative responses are comparable with H-2K^b specific responses in non-transgenic mice, even in the absence of exogenous IL-2. Thus, expression of H-2K^b molecules under control of human β-globln transcriptional control elements In transgenic mice is tolerogenlc but does not result in elimination of all H-2K^b reactive T cells from the mature repertoire. This suggests that tolerance In these mice may arise due to functional inactivation of H-2K^b reactive T cells in vivo when they encounter H-2K^b molecules expressed on cells of erythroid cell lineages or on non-erythroid cells which express H-2K^b molecules at very low levels or in a developmentally regulated pattern. Furthermore, In spite of the failure to detect H-2K^b expression on non-erythrold cells In these mice, we conclude that H-2K^b molecules participate In positive selection of the T cell repertoire since H-2K^b restricted T cell responses can be generated in these transgenic mice.