Thymocyte selection is regulated by the helix-loop-helix inhibitor protein, Id3.
E2A, HEB, E2-2, and daughterless are basic helix-loop-helix (bHLH) proteins that play key roles in multiple developmental pathways. The DNA binding activity of E2A, HEB, and E2-2 is regulated by a distinct class of inhibitor HLH proteins, the Id gene products. Here, we show that Id3 is required for major histocompatability (MHC) class I- and class II-restricted thymocyte positive selection. Additionally, H-Y TCR-mediated negative selection is severely perturbed in Id3 null mutant mice. Finally, we show that E2A and Id3 interact genetically to regulate thymocyte development. These observations identify the HLH inhibitory protein Id3 as an essential component required for proper thymocyte maturation.
Rivera
R R
RR
Department of Biology, 0366 University of California, San Diego, La Jolla 92093, USA.
Johns
C P
CP
Quan
J
J
Johnson
R S
RS
Murre
C
C
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology; D002454:Cell Differentiation; D005260:Female; D015870:Gene Expression; D018257:Helix-Loop-Helix Motifs; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D051796:Inhibitor of Differentiation Proteins; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009363:Neoplasm Proteins; D011946:Receptors, Antigen / Q000235:genetics / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
C028507:H-Y antigen receptor; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D051796:Inhibitor of Differentiation Proteins; D009363:Neoplasm Proteins; D011946:Receptors, Antigen; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014157:Transcription Factors; C075640:ID3 protein, human