Disrupted development of thymocytes expressing a transgenic TCR upon CD4 overexpression.
CD4 assists in T cell recognition of peptides bound to MHC class II molecules by binding to a non-polymorphic region on class II and stabilizing TCR recognition of the peptide-class II complex. Overexpression of CD4 in transgenic mice expressing a class II-restricted TCR resulted in a dramatic loss of thymocytes that became evident soon after the TCR and CD4 were co-expressed. Both the thymus and lymph nodes of the double-transgenic mice had reduced numbers of CD4 lineage T cells. A large proportion of the remaining CD4 lineage T cells lost either the transgenic TCR alpha or beta chains. The double-transgenic mice continued to generate thymocytes and T cells that expressed the transgenic TCR, but these cells did not express endogenous CD4. Overexpression of CD4 thus severely disrupts the normal developmental pathway of these thymocytes, supporting a model in which avidity of the TCR complex for self class II molecules determines the outcome of thymocyte development.
Davis
C B
CB
Division of Molecular Pathogenesis, Skirball Institute of Biomolecular Medicine, New York, NY 10016, USA.
Littman
D R
DR
D000818:Animals; D015704:CD4 Antigens / Q000235:genetics*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D005260:Female; D015870:Gene Expression; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D008954:Models, Biological; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D015704:CD4 Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta