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Regulation of T‐cell receptor β‐chain gene assembly by recombination signals: the beyond 12/23 restriction
Author(s) -
Tillman Robert E.,
Wooley Andrea L.,
Hughes Maureen M.,
Khor Bernard,
Sleckman Barry P.
Publication year - 2004
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.0105-2896.2004.00156.x
Subject(s) - biology , recombination , gene , genetics , receptor , computational biology , microbiology and biotechnology
Summary: Assembly of antigen receptor genes is regulated in several important contexts during lymphocyte development. This regulation occurs through modulation of gene segment accessibility to the V(D)J recombinase and/or at the level of the recombination reaction due, in part, to constraints imposed by recombination signal (RS) sequences. RSs are composed of conserved heptamer and nonamer sequences that flank relatively non‐conserved spacer sequences of either 12 or 23 base pairs. Recombination occurs only between RSs of dissimilar spacer lengths, a restriction known as the 12/23 rule. Recently, we have shown that RSs can impose significant constraints on antigen receptor gene assembly beyond enforcing the 12/23 rule. This restriction, termed B12/23, was revealed by analysis of T‐cell receptor β (TCRβ) locus rearrangements, where Dβ 12RSs and not Jβ 12RSs are capable of efficiently targeting Vβ 23RSs' rearrangement. The B12/23 restriction occurs at or prior to the DNA‐cleavage step of the V(D)J recombination reaction, relies on features of the Dβ 12RSs and Vβ 23RSs, and is not absolutely dependent on lymphoid‐specific factors other than the recombinase‐activating gene‐1 (RAG‐1) and RAG‐2 proteins. By preserving Dβ gene segment utilization, the B12/23 restriction is required, at a minimum, for the generation of a diverse repertoire of TCRβ chains.