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The Journal of Immunology, 1998, 160: 3883-3890.
Copyright © 1998 by The American Association of Immunologists

Posttranslational Regulation of TCR V{alpha} Allelic Exclusion During T Cell Differentiation1

S. Munir Alam and Nicholas R. J. Gascoigne2

Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037

We have previously shown that phenotypic allelic exclusion of TCR {alpha}-chain is functional only in mature thymocytes. A significant proportion of immature thymocytes (TCRlow) express more than one cell surface {alpha}-chain, but mature thymocytes (TCRhigh) show phenotypic allelic exclusion and express only a single {alpha}-chain. We have analyzed thymocytes for both surface and intracellular {alpha}-chain expression and find that the majority of mature thymocytes express a second {alpha}-chain intracellularly. This result is predicted by a model in which the developmentally regulated allelic exclusion of the TCR {alpha}-chain is caused by competition between {alpha}-chains for the ß-chain rather than by models in which one {alpha}-chain is down-regulated or in which selection favors cells with only a single {alpha}-chain species. Changes in the relative amounts of {alpha}- and ß-chains available for pairing may therefore allow competition between the two {alpha}-chains for the ß-chain. Peripheral T cells also frequently express second {alpha}-chains in the cytoplasm (18–27%), despite a rather low frequency of dual {alpha}-chain expression on the cell surface (2–4%). The frequency of nonsurface expressed {alpha}-chains is reduced somewhat compared with thymocytes, indicating that an additional level of control of allelic exclusion operates during the maturation of peripheral T cells.




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