TCR-alpha CDR3 loop audition regulates positive selection

Abstract

How positive selection molds the T cell repertoire has been difficult to examine. In this study, we use TCR-β-transgenic mice in which MHC shapes TCR-α use. Differential AV segment use is directly related to the constraints placed on the composition of the CDR3 loops. Where these constraints are low, efficient selection of αβ pairs follows. This mode of selection preferentially uses favored AV-AJ rearrangements and promotes diversity. Increased constraint on the α CDR3 loops leads to inefficient selection associated with uncommon recombination events and limited diversity. Further, the two modes of selection favor alternate sets of AJ segments. We discuss the relevance of these findings to the imprint of self-MHC restriction and peripheral T cell activation.