A Novel Multigene Family Encodes Diversified Variable Regions

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 96; no. 26; pp. 15080 - 15085
• Main Authors: Strong, Scott J., Mueller, M. Gail, Litman, Ronda T., Hawke, Noel A., Haire, Robert N., Miracle, Ann L., Rast, Jonathan P., Amemiya, Chris T., Litman, Gary W.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 21.12.1999; National Acad Sciences; National Academy of Sciences; The National Academy of Sciences
• Series: From the Cover
• Subjects: Amino Acid Sequence; Amino acids; Animals; Biological Sciences; Cells; Complementary DNA; DNA, Complementary - genetics; Evolution; Evolution, Molecular; Exons; Fishes - genetics; Fishes - immunology; Genes; Genes, Immunoglobulin; Genes, T-Cell Receptor; Genetic variation; Genomics; Immunoglobulin Variable Region - genetics; Immunology; Lymphoid Tissue - cytology; Molecular Sequence Data; Multigene Family; Phylogeny; Polymerase Chain Reaction; Receptors; Receptors, Immunologic - genetics; Regional identity; Sequence Homology, Amino Acid; Spheroides nephelus; Spleen; Stem Cells; T cell antigen receptors
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.96.26.15080

Antigen recognition in the adaptive immune response by lg and T-cell antigen 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 single 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 distinct from the C1 domains found in lg and TCR. Immunoreceptor tyrosine-based inhibitory motifs that transduce negative regulatory signals through the 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 genomic approach by using the pufferfish (Spheroides nephelus) to characterize a nonrearranging novel immune-type receptor gene family. Twenty-six different nonrearranging genes, which each encode highly diversified V as well as a V-like C2 extracellular domain, a transmembrane region, and in most instances, an immunoreceptor tyrosine-based inhibitory motif-containing cytoplasmic tail, are identified in an ≈ 113 kb P1 artificial chromosome insert. The presence in novel immune-type receptor genes of V regions that 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.