Allelic exclusion at the TCRbeta locus.
Assembly of TCRbeta chain variable-region genes is regulated in the context of allelic exclusion. Differential epigenetic modifications of the two TCRbeta alleles established early in embryonic development may be important for permitting allelic exclusion by ordering rearrangement of the two alleles in double-negative thymocytes. Expression of a TCRbeta chain, as part of the pre-TCR complex, activates signaling pathways that enforce allelic exclusion in double-positive thymocytes. These signaling pathways, which utilize p56(lck) and SLP-76, may be distinct from those used to promote other processes initiated by pre-TCR expression. In double-positive thymocytes allelic exclusion is enforced, in part, by changes in Vbeta gene segment accessibility promoted by cis-acting elements that may be distinct from those regulating accessibility of D/Jbeta gene segments.
Khor
Bernard
B
Washington University School of Medicine, Department of Pathology and Immunology, 660 South Euclid Avenue, Campus Box 8118, St. Louis, MO 63110-1093, USA. Khorb@medicine.wustl.edu
Sleckman
Barry P
BP
D000483:Alleles; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D015329:Gene Rearrangement, T-Lymphocyte / Q000502:physiology*; D019674:Genes, T-Cell Receptor beta / Q000502:physiology*; D006801:Humans; D013601:T-Lymphocytes / Q000166:cytology / Q000502:physiology