Genetic modulation of T cell receptor gene segment usage during somatic recombination

被引:44
作者
Livak, F
Burtrum, DB
Rowen, L
Schatz, DG
Petrie, HT
机构
[1] Mem Sloan Kettering Canc Ctr, Program Immunol, New York, NY 10021 USA
[2] Yale Univ, Sch Med, Immunobiol Sect, New Haven, CT USA
[3] Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT USA
[4] Cornell Univ, Joan & Sanford Weill Grad Sch Med Sci, New York, NY 10021 USA
[5] Univ Washington, Dept Mol Biotechnol, Seattle, WA 98195 USA
关键词
thymus; VDJ recombination; recombination signal sequence; T cell receptor beta locus; repertoire selection;
D O I
10.1084/jem.192.8.1191
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Lymphocyte antigen receptors are not encoded by germline genes, but rather are produced by combinatorial joining between clusters of gene segments in somatic cells. Within a given cluster, gene segment usage during recombination is thought to be largely random, with biased representation in mature T lymphocytes resulting from protein-mediated selection of a subset of the total repertoire. Here we show that T cell receptor D beta and J beta gene segment usage is not random, but is patterned at the time of recombination. The hierarchy of gene segment usage is independent of gene segment proximity, but rather is influenced by the ability of the nanking recombination signal sequences (RSS) to bind the recombinase and/or to form a paired synaptic complex. Importantly, the relative frequency of gene segment usage established during recombination is very similar to that found after protein-mediated selection, suggesting that in addition to targeting recombinase activity, the RSS may have evolved to bias the naive repertoire in favor of useful gene products.
引用
收藏
页码:1191 / 1196
页数:6
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