Ordered and coordinated rearrangement of the TCR alpha locus: role of secondary rearrangement in thymic selection.
The Ag receptor of the T lymphocyte is composed of an alphabeta heterodimer. Both alpha- and beta-chains are products of the somatic rearrangement of V(D)J segments encoded on the respective loci. During T cell development, beta-chain rearrangement precedes alpha-chain rearrangement. The mechanism of allelic exclusion ensures the expression of a single beta-chain in each T cell, whereas a large number of T cells express two functional alpha-chains. Here we demonstrate evidence that TCR alpha rearrangement is initiated by rearranging a 3' Valpha segment and a 5' Jalpha segment on both chromosomes. Rearrangement then proceeds by using upstream Valpha and downstream Jalpha segments until it is terminated by successful positive selection. This ordered and coordinated rearrangement allows a single thymocyte to sequentially express multiple TCRs with different specificities to optimize the efficiency of positive selection. Thus, the lack of allelic exclusion and TCR alpha secondary rearrangement play a key role in the formation of a functional T cell repertoire.
Huang
C
C
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Kanagawa
O
O
D000483:Alleles; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D005819:Genetic Markers / Q000276:immunology; D006825:Hybridomas; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D005819:Genetic Markers; D016693:Receptors, Antigen, T-Cell, alpha-beta