Posttranslational regulation of TCR Valpha allelic exclusion during T cell differentiation.
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 beta-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 beta-chains available for pairing may therefore allow competition between the two alpha-chains for the beta-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.
Alam
S M
SM
Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Gascoigne
N R
NR
D000483:Alleles; D000818:Animals; D002454:Cell Differentiation; D002462:Cell Membrane / Q000276:immunology; D003593:Cytoplasm / Q000276:immunology; D018507:Gene Expression Regulation, Developmental; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008954:Models, Biological; D010641:Phenotype; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology