A novel multigene family encodes diversified variable regions

Antigen recognition in the adaptive immune response by Ig and T-cell antige n receptors (TCRs) is effected through patterned differences in the peptide sequence in the V regions. V-region specificity forms through genetically programmed rearrangement of individual, diversified segmental elements in s ingle somatic cells. Other lg superfamily members, including natural killer receptors that mediate cell-surface recognition, do not undergo segmental reorganization, and contain type-2 C (C2) domains, which are structurally d istinct from the C1 domains found in lg and TCR, Immunoreceptor tyrosine-ba sed inhibitory motifs that transduce negative regulatory signals through th e cell membrane are found in certain natural killer and other cell surface inhibitory receptors, but not in lg and TCR. In this study, we employ a gen omic approach by using the pufferfish (Spheroides nephelus) to characterize a nonrearranging novel immune-type receptor gene family. Twenty-six differ ent nonrearranging genes, which each encode highly diversified V as well as a V-like C2 extracellular domain, a transmembrane region, and in most inst ances, an immunoreceptor tyrosine-based inhibitory motif-containing cytopla smic tail, are identified in an approximate to 113 kb p1 artificial chromos ome insert. The presence in novel immune-type receptor genes of V regions t hat are related closely to those found in lg and TCR as well as regulatory motifs that are characteristic of inhibitory receptors implies a heretofore unrecognized link between known receptors that mediate adaptive and innate immune functions.