Coreceptor-independent T cell activation in mice expressing MHC class II molecules mutated in the CD4 binding domain.
We have previously reported that efficient selection of the mature CD4+ T cell repertoire requires a functional interaction between the CD4 coreceptor on the developing thymocyte and the MHC class II molecule on the thymic epithelium. Mice expressing a class II protein carrying the EA137/VA142 double mutation in the CD4 binding domain develop fewer than one-third the number of CD4+ T cells found in wild-type mice. In this report we describe the functional characteristics of this population of CD4+ T cells. CD4+ T cells that develop under these conditions are predicted to be a CD4-independent subset of T cells, bearing TCRs of sufficient affinity for the class II ligand to undergo selection despite the absence of accessory class II-CD4 interactions. We show that CD4+ T cells from the class II mutant mice are indeed CD4 independent in their peripheral activation requirements. Surprisingly, we find that CD4+ T cells from the class II mutant mice, having been selected in the absence of a productive class II-CD4 interaction, fail to functionally engage CD4 even when subsequently provided with a wild-type class II ligand. Nevertheless, CD4+ T cells from EA137/VA142 class II mutant mice can respond to T-dependent Ags and support Ig isotype switching.
Mostaghel
E A
EA
Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
Riberdy
J M
JM
Steeber
D A
DA
Doyle
C
C
D000818:Animals; D001665:Binding Sites; D015704:CD4 Antigens / Q000276:immunology / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D017637:Clonal Deletion; D006433:Hemocyanins / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D017578:Immunoglobulin Class Switching; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D016297:Mutagenesis, Site-Directed; D010047:Ovalbumin / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D015704:CD4 Antigens; D000949:Histocompatibility Antigens Class II; D010047:Ovalbumin; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin