Competitive displacement of pT alpha by TCR-alpha during TCR assembly prevents surface coexpression of pre-TCR and alpha beta TCR.
During alphabeta T cell development, CD4(-)CD8(-) thymocytes first express pre-TCR (pTalpha/TCR-beta) before their differentiation to the CD4(+)CD8(+) stage. Positive selection of self-tolerant T cells is then determined by the alphabeta TCR expressed on CD4(+)CD8(+) thymocytes. Conceivably, an overlap in surface expression of these two receptors would interfere with the delicate balance of thymic selection. Therefore, a mechanism ensuring the sequential expression of pre-TCR and TCR must function during thymocyte development. In support of this notion, we demonstrate that expression of TCR-alpha by immature thymocytes terminates the surface expression of pre-TCR. Our results reveal that expression of TCR-alpha precludes the formation of pTalpha/TCR-beta dimers within the endoplasmic reticulum, leading to the displacement of pre-TCR from the cell surface. These findings illustrate a novel posttranslational mechanism for the regulation of pre-TCR expression, which may ensure that alphabeta TCR expression on thymocytes undergoing selection is not compromised by the expression of pre-TCR.
Trop
S
S
Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
Rhodes
M
M
Wiest
D L
DL
Hugo
P
P
Zúñiga-Pflücker
J C
JC
D000818:Animals; D001667:Binding, Competitive / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D019281:Dimerization; D004220:Disulfides / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology; D019673:Genes, T-Cell Receptor alpha / Q000502:physiology; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D008822:Mice, Transgenic; D011498:Protein Precursors / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D004220:Disulfides; D008562:Membrane Glycoproteins; D011498:Protein Precursors; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta; C090377:pre-T cell receptor alpha