Competitive displacement of pT alpha by TCR-alpha during TCR assembly prevents surface coexpression of pre-TCR and alpha beta TCR.
Copyright policy )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.
- University of Toronto Canada
Mice, Knockout, Membrane Glycoproteins, Receptors, Antigen, T-Cell, alpha-beta, Cell Membrane, Cell Differentiation, Mice, Transgenic, Mice, SCID, Binding, Competitive, Mice, Inbred C57BL, Mice, Gene Expression Regulation, T-Lymphocyte Subsets, Animals, Disulfides, RNA, Messenger, Protein Precursors, Dimerization, Protein Processing, Post-Translational, Cells, Cultured, Genes, T-Cell Receptor alpha
Mice, Knockout, Membrane Glycoproteins, Receptors, Antigen, T-Cell, alpha-beta, Cell Membrane, Cell Differentiation, Mice, Transgenic, Mice, SCID, Binding, Competitive, Mice, Inbred C57BL, Mice, Gene Expression Regulation, T-Lymphocyte Subsets, Animals, Disulfides, RNA, Messenger, Protein Precursors, Dimerization, Protein Processing, Post-Translational, Cells, Cultured, Genes, T-Cell Receptor alpha
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