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-Chain Rearrangement Is Followed by Selection for Shorter TCR ß-Chain Complementarity-Determining Region 31
The Blood Research Institute, The Blood Center of Southeastern Wisconsin, Milwaukee WI 53201
Thymocyte maturation consists of a number of stages, the goal of
which is the production of functioning T cells that respond to foreign
antigenic peptides using their clonotypic receptors. Selection of a
productively rearranged TCR ß-chain is the first stage in the process
and occurs at the double-negative to double-positive (DP) transition.
Later maturation stages are based on changes in markers such as CD5,
CD69, or IL-7R. A stage in which 
-chains are selected has also been
identified using ß-chain transgenic mice. Here we identify two
additional selection stages in human thymocytes based on
characteristics of the TCR. selection is measured directly by
identification of in-frame rearrangements and is associated with the
appearance of CD3 on the DP thymocyte surface. The next stage has not
yet been described and involves selection of thymocytes that express
shorter TCR ß-chain complementarity-determining region 3 (CDR3). This
stage is associated with the acquisition of high levels of CDR3 by DP
cells and the transition to SP thymocytes. The extent of CDR3 length
selection observed is a function of the TCR V and J genes. We propose
that CDR3 length selection is based on recognition of the MHC.
Thus, there exist limitations on the allowable length of that portion
of the TCR most intimately in contact with MHC and peptide. This may be
a physical representation of positive selection.
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