Variable domains in hagfish: NICIR is a polymorphic multigene family expressed preferentially in leukocytes and is related to lamprey TCR-like.

The jawless vertebrates, represented by hagfish and lampreys, are the most advanced animals that apparently lack T cell and B cell receptors. As such, they offer unique opportunities for understanding the evolution of antigen receptors and variable (V)-type immunoglobulin (Ig)-like domains. In the present study, we describe four hagfish Ig superfamily (IgSF) members carrying V-type domains. None of them appeared to have direct counterparts in jawed vertebrates, indicating that many IgSF molecules have either evolved independently in jawed and jawless vertebrates or diverged to the extent that clear homology is no longer recognizable. One of the members encoded a molecule closely related to the previously described membrane protein designated novel ITAM (immunoreceptor tyrosine-based activation motif)-containing IgSF receptors (NICIR). We show here that NICIR is a polymorphic multigene family with at least three members and is expressed predominantly in peripheral blood leukocytes. Phylogenetic analysis indicates that among known proteins, NICIR is most closely related to the lamprey molecule recently proposed to be a potential ancestor of T cell receptors.