Molecular genetics at the T-Cell receptor βlocus: Insights into the regulation of V(D)J recombination

Abstract

The V(D)J recombination machinery assembles antigen receptor genes from germline V,D and J segments during lymphocyte development. InαβT cells, this leads to the production of the T-cell receptor (TCR) a and Pchains. Notably, V(D)J recombination at the Tcrb locus is tightly controlled at various levels, includingcell-type and stagespecificities, intralocus orderingand allelic exclusion. Although many of these controls are partly mediated at the level of genomic accessibility to the V(D)J recombinase, recent studies have uncovered novel mechanisms that are also likely to contribute to the developmental regulation of Tcrb gene rearrangement events. In this chapter, we summarize our current knowledge and highlight unanswered questions regarding the regulation of V(D)J recombinationat the Tcrb locus, placingemphasis on mouse transgenesis and gene-targeting approaches. © 2009 Landes Bioscience and Springer Science+Business Media.