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Locus: Role of Secondary Rearrangement in Thymic Selection1
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110
The Ag receptor of the T lymphocyte is composed of an 
heterodimer. Both - and -chains are products of the somatic
rearrangement of V(D)J segments encoded on the respective loci. During
T cell development, -chain rearrangement precedes -chain
rearrangement. The mechanism of allelic exclusion ensures the
expression of a single -chain in each T cell, whereas a large number
of T cells express two functional -chains. Here we demonstrate
evidence that TCR rearrangement is initiated by rearranging a 3'
V segment and a 5' J segment on both chromosomes. Rearrangement
then proceeds by using upstream V and downstream J segments until
it is terminated by successful positive selection. This ordered and
coordinated rearrangement allows a single thymocyte to sequentially
express multiple TCRs with different specificities to optimize the
efficiency of positive selection. Thus, the lack of allelic exclusion
and TCR secondary rearrangement play a key role in the formation of
a functional T cell repertoire.
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