Expanding our understanding of immunoglobulin, T-cell antigen receptor, and novel immune-type receptor genes: a subset of the immunoglobulin gene superfamily

The immunoglobulin superfamily (IgSF) is an extensively diversified multige ne family whose members share a common structural feature, the Ig fold. Mem bers of the Ig/T-cell antigen receptor (TCR) subset of the IgSF mediate ant igen-specific recognition in adaptive immune responses. Antigen-binding rec eptors belonging to this subset are present in all species of jawed vertebr ates. To explore whether there are additional structurally related but othe rwise distinct members of this subset, we have developed a technique termed the short-primer polymerase chain reaction (PCR) that targets structurally conserved short motifs in the Ig fold. Large-scale sequencing efforts and recent advances in information biotechnology, including "electronic PCR," p rovide additional computational means to implement similarly directed searc hes within databases. The use of these approaches has led to the discoverie s of Ig/TCR homologues in a variety of phylogenetically diverse organisms, a diversified family of novel immune-type receptor genes, as well as a nove l human IgSF member. The potential of random sequencing efforts and virtual screening of databases is described in the context of two novel genes in b ony fish. The various methodologies that are discussed and the examples sho wn provide means for further investigating and/or elucidating novel IgSF re ceptors as well as components of pathways that are involved in immune respo nses in both traditional and nontraditional model systems.