| Abstract: |
Allelic exclusion of immune receptor genes (and molecules) is incompletely understood. With regard to TCRαβ lineage T cells, exclusion at the tcr-b, but not tcr-a, locus seems to be strictly controlled at the locus rearrangement level. Consequently, while nearly all developing TCRαβ thymocytes express a single TCRβ protein, many thymocytes rearrange and express two different TCRα chains and, thus, display two αβTCRs on the cell surface. Of interest, the number of such deal TCR-expressing cells is appreciably lower among the mature T cells. To understand the details of TCR chain regulation at various stages of T cell development, we analyzed TCR expression in mice transgenic for two rearranged αβTCR. We discovered that in such TCR double-transgenic (TCRdTg) mice peripheral T cells were functionally monospeciflc. Molecularly, this monospecificity was due to TCRα exclusion: one transgenic TCRα protein was selectively down-regulated from the thymocyte and T cell surface. In searching for the mechanism(s) governing this selective TCRα down-regulation, we present evidence for the role of protein tyrosine kinase signaling and coreceptor involvement. This mechanism may be operating in normal thymocytes. |
| Keywords: |
signal transduction; controlled study; nonhuman; t lymphocyte; cd8-positive t-lymphocytes; t-lymphocytes; animal cell; mouse; animals; mice; mice, knockout; cell maturation; down-regulation; cell differentiation; protein tyrosine kinase; mice, inbred balb c; mice, inbred c57bl; cell lineage; transgenic mouse; mice, transgenic; immunophenotyping; protein-tyrosine kinases; thymocyte; receptors, antigen, t-cell, alpha-beta; t lymphocyte receptor alpha chain; cell surface; receptor down regulation; genes, dominant; male; female; priority journal; article; gene rearrangement, alpha-chain t-cell antigen receptor; genes, t-cell receptor alpha
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