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Accessibility control of variable region gene assembly during T‐cell development
Author(s) -
Sleckman Barry P.,
Bassing Craig H.,
Bardon Christiana G.,
Okada Ami,
Khor Bernard,
Bories JeanChristophe,
Monroe Robert,
Alt Frederick W.
Publication year - 1998
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/j.1600-065x.1998.tb01235.x
Subject(s) - t cell receptor , allelic exclusion , biology , gene , genetics , locus (genetics) , v(d)j recombination , recombination activating gene , gene rearrangement , t cell , context (archaeology) , recombination , immune system , paleontology
Summary: 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 of either an αβ or γδ T‐cell antigen receptor (TCR), The genes that encode the TCR β and y chains lie in distinct loci, whereas the genes that encode the TCR a and S chains he in a single locos (TCR α/δ locus). Assembly of TCR variable region genes is mediated by a site‐specific recombination process that is common among all lymphocytes. Despite the common nature of this process, recombination of TCR genes is tightly regulated within the context of the developing T cell. TCR β, γ and δ variable region genes are assembled prior to TCR α variable region genes. Furthermore, assembly of TCR β variable region genes is regulated within the context of allelic exclusion. The regulation of rearrangement arid expression of genes within the TCR α/δ locus presents a complicated problem. TCR α and δ variable region genes are assembled at different stages of T‐cell development, and fully assembled TCR α and δ variable region genes must be expressed in distinct hneages of T cells, αβ and γδ. respectively We have developed several experimental approaches lo assess the role of cis‐acting elements in regulating recombination and expression of TCR genes. Here we describe these approaches and discuss our analyses of the regulation of accessibility of the TCR β and TCR α/δ foci during T‐cell development.