A NEW ANTIGEN RECEPTOR GENE FAMILY THAT UNDERGOES REARRANGEMENT AND EXTENSIVE SOMATIC DIVERSIFICATION IN SHARKS

IMMUNOGLOBULIN and T-cell receptor (TCR) molecules are central to the adaptive immune system, Sequence conservation, similarities in domain structure, and usage of similar recombination signal sequences and rec ombination machinery indicate that there was probably a time during ev olution when an ancestral receptor diverged to the modern-day immunogl obulin and TCR(1-3). Other molecules that undergo rearrangement have n ot been described in vertebrates, nor have intermediates been identifi ed that have features of both these gene families, We report here the isolation of a new member of the immunoglobulin superfamily from the n urse shark, Ginglymostoma cirratum, which contains one variable and fi ve constant domains and is found as a dimer in serum. Analyses of comp lementary DNA clones show extensive sequence diversity within variable domains, which is generated by both rearrangement and somatic diversi fication mechanisms, Our results suggest that rearranging loci distinc t from immunoglobulin and TCR have arisen during evolution.