In jawless vertebrates, variable lymphocyte receptors of two types, VLRA and VLRB, are reciprocally expressed by lymphocytes that resemble the T cells and B cells of jawed vertebrates. In Nature, Hirano et al. define another lineage of T cell–like lymphocytes that express the related VLRC receptors. Assembly of VLRC and VLRA occurs in the 'thymoid' organ. VLRA+ and VLRC+ cells have overlapping but distinct gene-expression profiles, with VLRA+ cells expressing the transcription factor TCF-1 and VLRC+ cells expressing the transcription factor SOX13. Both VLRA+ and VLRC+ cells proliferate after antigen stimulation and 'preferentially' populate the intestinal epithelium but do not differentiate into VLR-secreting cells. VLRC+ cells are the main lymphocyte population in the lamprey epithelium, where they express a repertoire more restricted than that of other tissues. This suggests that having two distinct T cell lineages is a basic principle for a lymphocyte-based adaptive immune system.

Nature (11 August 2013) doi:10.1038/nature12467