VLRs

VLRs, or variable lymphocyte receptors, are a family of antigen receptors used by jawless vertebrates such as lampreys and hagfish. They form a distinct, evolutionarily ancient system of adaptive immunity that relies on leucine-rich repeat (LRR) modules rather than the immunoglobulin-based receptors found in jawed vertebrates.

The VLR gene family includes three main lineages—VLR-A, VLR-B, and VLR-C—each encoded at separate loci and expressed on different lymphocyte-like cells. VLR-B is typically associated with B-like cells and acts as a B-cell receptor, while VLR-A is linked to T-like cells; VLR-C expression varies among species. Diversity within these receptors arises not from VDJ-type rearrangements, but from somatic assembly of incomplete germline VLR genes through the integration of LRR-encoding cassettes. This somatic assembly generates a vast repertoire of receptor specificities capable of recognizing a wide array of pathogens.

On the cell surface, VLRs bind antigens and trigger clonal expansion of the responding lymphocytes, enabling targeted immune responses. The system supports broad pathogen recognition and offers a form of immune memory that has been observed as memory-like responses in lamprey VLRs. Compared with the Ig-based adaptive immunity of jawed vertebrates, VLR-based immunity represents a distinct evolutionary solution to antigen recognition and defense.

Significance lies in showing that adaptive immunity can arise via different molecular frameworks. Ongoing research seeks to clarify the precise molecular machinery behind VLR diversification, signaling, and the full range of functional roles across jawless vertebrates.