||The adaptive immune system in jawed vertebrates features the generation of diverse T and B cell repertoires of anticipatory receptors through V(D)J rearrangement. We have found that living representatives of the jawless vertebrates, lamprey and hagfish, also generate a very large repertoire of variable lymphocyte receptors (VLR). However, unlike BCR and TCR, the VLR proteins are composed of multiple leucine rich repeats (LRR), a stalk region, and a glycosyl-phosphatityl-inositol anchor that tethers them to the lymphocyte surface. Differences in numbers and sequences of the constituent LRRs account for the VLR diversity. Mature VLR genes are created through a multistep assembly process that involves a random modular insertion of different LRR coding sequences into an incomplete germline VLR gene.
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