Transgenic HLA-DR alpha faithfully reconstitutes IE-controlled immune functions and induces cross-tolerance to E alpha in E alpha 0 mutant mice.
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.
Lawrance
S K
SK
Department of Immunology IMM8, Research Institute of Scripps Clinic, La Jolla, California 92037.
Karlsson
L
L
Price
J
J
Quaranta
V
V
Ron
Y
Y
Sprent
J
J
Peterson
P A
PA
D000818:Animals; D005796:Genes; D005816:Genetic Complementation Test; D006684:HLA-DR Antigens / Q000235:genetics* / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D007959:Lymphocyte Culture Test, Mixed; D046911:Macromolecular Substances; D051379:Mice; D008822:Mice, Transgenic; D011485:Protein Binding; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000276:immunology; D014018:Tissue Distribution
D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D046911:Macromolecular Substances; D011948:Receptors, Antigen, T-Cell