ACCESSIBILITY CONTROL OF VARIABLE REGION GENE ASSEMBLY DURING T-CELL DEVELOPMENT

T-cell development is a complex and ordered process that is regulated in part by the progressive assembly and expression of antigen receptor genes. T cells can be divided into two lineages based on expression o f either an alpha beta or gamma delta T-cell antigen receptor (TCR). T he genes that encode the TCR beta and gamma chains lie in distinct loc i, whereas the genes that encode the TCR alpha and delta chains lie in a single locus (TCR alpha/delta locus). Assembly of TCR variable regi on genes is mediated by a site-specific recombination process that is common among all lymphocytes. Despite the common nature of this proces s, recombination of TCR genes is tightly regulated within the context of the developing T cell. TCR beta, gamma and delta variable region ge nes are assembled prior to TCR a variable region genes. Furthermore, a ssembly of TCR beta variable region genes is regulated within the cont ext of allelic exclusion. The regulation of rearrangement and expressi on of genes within the TCR alpha/delta locus presents a complicated pr oblem. TCR alpha and delta variable region genes are assembled at diff erent stages of T-cell development, and fully assembled TCR alpha and delta variable region genes must be expressed in distinct Lineages of T cells, alpha beta and gamma delta, respectively We have developed se veral experimental approaches to assess the role of cis-acting element s in regulating recombination and expression of TCR genes. Here we des cribe these approaches and discuss our analyses of the regulation of a ccessibility of the TCR beta and TCR alpha/delta loci during T-cell de velopment.