Phenotype and function of CD4+ T cells in mice lacking invariant chain.
Mice bearing a targeted disruption of the gene encoding the invariant chain (Ii) have provided a deeper understanding of the critical role that Ii plays in the assembly, transport, and peptide occupancy of MHC class II molecules. In this study, we have investigated the consequence of the altered class II expression in Ii-deficient (Ii zero) mice on the phenotype and function of their CD4+ T cells. As seen by others, these mice show a sharp reduction in the CD4+8- subset in the thymus and periphery. Furthermore, a large proportion of the peripheral CD4+, but not CD8+, T cells in Ii zero mice exhibit decreased surface TCR-alpha beta levels and express markers of T cell activation. Although the CD4+ T cells respond to mitogens, anti-CD3 mAbs, and alloantigens, they respond poorly to the bacterial superantigen staphylococcal enterotoxin B and do not respond to peptide and protein Ags. Analysis of reciprocal radiation bone marrow chimeras constructed using Ii zero and wild-type mice indicate that the lack of Ii in the thymus is responsible for the phenotype of the CD4+ T cells in mutant mice. These results suggest that the altered thymic peptide repertoire displayed by class II molecules in the absence of Ii has a dramatic impact on the selection of CD4+ T cells and their phenotype in the periphery.
Wong
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Howard Hughes Medical Institute, Department of Immunology, University of Washington School of Medicine, Seattle 98195, USA.
Rudensky
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D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics* / Q000276:immunology; D016026:Bone Marrow Transplantation; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000145:classification / Q000187:drug effects / Q000276:immunology*; D003208:Concanavalin A / Q000494:pharmacology; D004768:Enterotoxins / Q000276:immunology; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000276:immunology; D016130:Immunophenotyping; D007519:Isoantigens / Q000276:immunology; D008198:Lymph Nodes; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000276:immunology; D011828:Radiation Chimera; D013211:Staphylococcus aureus / Q000276:immunology; D018089:Superantigens / Q000276:immunology
D000911:Antibodies, Monoclonal; D000944:Antigens, Differentiation, B-Lymphocyte; D017252:CD3 Complex; D004768:Enterotoxins; D000949:Histocompatibility Antigens Class II; D007519:Isoantigens; D010455:Peptides; D018089:Superantigens; C045084:invariant chain; D003208:Concanavalin A; C031818:enterotoxin B, staphylococcal