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A novel multigene family encodes diversified variable regions

Strong, Scott J. and Mueller, M. Gail and Litman, Ronda T. and Hawke, Noel A. and Haire, Robert N. and Miracle, Ann L. and Rast, Jonathan P. and Amemiya, Chris T. and Litman, Gary W. (1999) A novel multigene family encodes diversified variable regions. Proceedings of the National Academy of Sciences of the United States of America, 96 (26). pp. 15080-15085. ISSN 0027-8424. PMCID PMC24776.

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Antigen recognition in the adaptive immune response by Ig 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 Ig 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 Ig 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 Ig 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 Ig 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.

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Additional Information:© 1999 The National Academy of Sciences. Edited by Martin G. Weigert, Princeton University, Princeton, NJ, and approved October 15, 1999 (received for review July 23, 1999). This paper was submitted directly (Track II) to the PNAS office. Data deposition: The sequences reported in this paper have been deposited in the GenBank database (accession nos. AF110144, AF110145, and AF094698). We thank Barbara Pryor for editorial assistance and Drs. David Schatz, Jeffrey Yoder, Louis Du Pasquier, Jim Kaufman, and Donald Wiley for valuable comments on this work. We also thank Dr. Eric Davidson for providing access to the Q-Bot robotics workstation. This work was supported by grants to G.W.L. from the National Institutes of Health, the Valerie Fund, and the Pediatric Cancer Foundation, and grants to C.T.A. from the National Institutes of Health and the National Science Foundation. The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. §1734 solely to indicate this fact.
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Pediatric Cancer FoundationUNSPECIFIED
Subject Keywords:V gene diversity; immunoreceptor tyrosine-based inhibitory motif; evolution; adaptive immunity; innate immunity
Issue or Number:26
PubMed Central ID:PMC24776
Record Number:CaltechAUTHORS:20141125-100556553
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Official Citation:Strong, S. J., Mueller, M. G., Litman, R. T., Hawke, N. A., Haire, R. N., Miracle, A. L., . . . Litman, G. W. (1999). A novel multigene family encodes diversified variable regions. Proceedings of the National Academy of Sciences, 96(26), 15080-15085. doi: 10.1073/pnas.96.26.15080
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:52135
Deposited By: Jason Perez
Deposited On:25 Nov 2014 21:36
Last Modified:03 Oct 2019 07:39

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