Novel immune-type receptor genes

Novel immune-type receptor (NITR) genes, which initially were identified in the Southern pufferfish (Spheroides nephelus), encode products which consi st of an extracellular variable (V) and V-like CZ (V/C2) domain, a transmem brane region, and a cytoplasmic tail, which typically possesses an immunore ceptor tyrosine-based inhibition motif (ITIM). Multiple NITR genes have bee n identified in close, contiguous chromosomal linkage. The V regions of NIT Rs resemble prototypic forms defined for immunoglobulin (Ig) and T-cell ant igen receptor (TCR), are present in multiple families and exhibit regionali zed variation in sequence, which also occurs in Ig and TCR. Comparisons of exons encoding transmembrane and cytoplasmic regions of multiple NITRs sugg est that exon shuffling has factored in the diversification of the NITR gen e complex. Zebrafish (Danio redo) NITRs exhibit many of these characteristi cs. NITRs that have been identified in additional species of bony fish demo nstrate additional variation in the number of extracellular domains as well as in the presence of intramembranous charged residues, cytoplasmic tails and ITIMs. The presence in NITRs of V regions that are related closely to t hose found in Ig and TCR, as well as regulatory motifs and other structural features that are characteristic of immune inhibitory receptors encoded at the leukocyte receptor duster, suggests that the NITRs are representative of an integral stage in the evolution of innate and adaptive immune functio n.