The cytoplasmic domain of CD4 promotes the development of CD4 lineage T cells.
Thymocytes must bind major histocompatibility complex (MHC) proteins on thymic epithelial cells in order to mature into either CD8+ cytotoxic T cells or CD4+ helper T cells. Thymic precursors express both CD8 and CD4, and it has been suggested that the intracellular signals generated by CD8 or CD4 binding to class I or II MHC, respectively, might influence the fate of uncommitted cells. Here we test the notion that intracellular signaling by CD4 directs the development of thymocytes to a CD4 lineage. A hybrid protein consisting of the CD8 extracellular and transmembrane domains and the cytoplasmic domain of CD4 (CD884) should bind class I MHC but deliver a CD4 intracellular signal. We find that expression of a hybrid CD884 protein in thymocytes of transgenic mice leads to the development of large numbers of class I MHC-specific, CD4 lineage T cells. We discuss these results in terms of current models for CD4 and CD8 lineage commitment.
Itano
A
A
Department of Molecular and Cell Biology, University of California, Berkeley, 94720, USA.
Salmon
P
P
Kioussis
D
D
Tolaini
M
M
Corbella
P
P
Robey
E
E
D000818:Animals; D001483:Base Sequence; D015704:CD4 Antigens / Q000096:biosynthesis / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D016827:CD8 Antigens / Q000096:biosynthesis / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology; D008285:Major Histocompatibility Complex; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009838:Oligodeoxyribonucleotides; D055503:Protein Multimerization; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000276:immunology; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013950:Thymus Gland
D015704:CD4 Antigens; D016827:CD8 Antigens; D015395:Histocompatibility Antigens Class I; D009838:Oligodeoxyribonucleotides; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins