Selection of the lamprey VLRC antigen receptor repertoire

The alternative adaptive immune system of jawless vertebrates is based on three types of variable lymphocyte receptors (VLRs) that are differentially expressed by distinct B- and T-like lymphocyte lineages. Like the antibodies and T-cell receptors of jawed vertebrates, the highly variable VLR antigen receptors are generated by combinatorial assembly. However, it is not known whether VLRs are subjected to selection to mitigate the detrimental effects of self-reactivity. Here, we identify signatures for selection of the VLRC receptors that are expressed by one of the T-cell lineages of lamprey; selection concerns the length of the receptor molecules and their N-terminal sequence diversity. These findings pave the way to identifying the mechanistic basis of selection.