Transgenic HLA-DR alpha faithfully reconstitutes IE-controlled immune functions and induces cross-tolerance to E alpha in E alpha 0 mutant mice.

Lawrance SK, Karlsson L, Price J, Quaranta V, Ron Y, Sprent J, Peterson PA
Cell. 1989 58 (3): 583-94

PMID: 2527088 · DOI:10.1016/0092-8674(89)90439-x

We have constructed transgenic mice that express the human class II MHC molecule HLA-DR alpha on a genetic background in which the equivalent endogenous gene, H-2 IE alpha, is not expressed. In these mice, DR alpha complemented the E beta chain such that tissue-specific expression of an interspecies hybrid DR alpha-E beta heterodimer was obtained. Despite 25% amino acid differences between DR alpha and E alpha, immune responsiveness to IE-controlled antigens, clonal deletion of IE-reactive T cells, and alloantigenicity were quantitatively and qualitatively indistinguishable in IE-positive mice and in mice that had integrated at least four copies of the transgene. These results demonstrate a remarkable degree of structural, regulatory, and functional conservation. They also suggest that tolerance induction involves only discrete portions of MHC molecules.

MeSH Terms (16)

Animals Genes Genetic Complementation Test Histocompatibility Antigens Class II HLA-DR Antigens Humans Immunity, Cellular Lymphocyte Culture Test, Mixed Macromolecular Substances Mice Mice, Transgenic Protein Binding Receptors, Antigen, T-Cell Structure-Activity Relationship T-Lymphocytes Tissue Distribution

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