Copy number and sequence variation of leucine-rich repeat modules suggests distinct functional constraints operating on variable lymphocyte receptors expressed by agnathan T cell-like and B cell-like lymphocytes.

Unlike jawed vertebrates that use T cell and B cell receptors for antigen recognition, jawless vertebrates represented by lampreys and hagfish use variable lymphocyte receptors (VLR) as antigen receptors. VLRs generate high levels of diversity by assembling variable leucine-rich repeat (LRR) modules. Of the three VLRs thus far identified, VLRB is expressed on B cell-like lymphocytes and functions as antibodies, whereas VLRA and VLRC are expressed on T cell-like lymphocytes and function as membrane-bound receptors. In the present study, we show that the copy number of LRRV modules in lamprey and hagfish VLRB transcripts follows a binominal distribution with the success rates of 15.5 and 22.4 %, respectively. By contrast, the copy number distribution of LRRV modules in VLRA and VLRC transcripts deviates from the binominal distribution mainly because transcripts with two or less LRRV modules occur infrequently. Notably, the second LRRV module shows distinctive sequence signatures in VLRA and VLRC, but not in VLRB transcripts. These observations suggest that distinct functional constraints operate on VLRs expressed by agnathan T cell-like and B cell-like lymphocytes.