pancer2004 - Somatic diversification of variable lymphocyte...

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Unformatted text preview: Somatic diversification of variable lymphocyte receptors in the agnathan sea lamprey Zeev Pancer 1,2 , Chris T. Amemiya 6 , Go ¨tz R. A. Ehrhardt 1,5 , Jill Ceitlin 7 , G. Larry Gartland 1,4 & Max D. Cooper 1,2,3,4,5 1 Division of Developmental and Clinical Immunology, Departments of 2 Medicine, 3 Pediatrics and 4 Microbiology, and the 5 Howard Hughes Medical Institute, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA 6 Molecular Genetics Program, Benaroya Research Institute at Virginia Mason, Seattle, Washington, 98101, USA 7 University of Michigan, Ann Arbor, Michigan 48109, USA ........................................................................................................................................................................................................................... Although jawless vertebrates are apparently capable of adaptive immune responses, they have not been found to possess the recombinatorial antigen receptors shared by all jawed vertebrates. Our search for the phylogenetic roots of adaptive immunity in the lamprey has instead identified a new type of variable lymphocyte receptors (VLRs) composed of highly diverse leucine-rich repeats (LRR) sandwiched between amino- and carboxy-terminal LRRs. An invariant stalk region tethers the VLRs to the cell surface by means of a glycosyl-phosphatidyl-inositol anchor. To generate rearranged VLR genes of the diversity necessary for an anticipatory immune system, the single lamprey VLR locus contains a large bank of diverse LRR cassettes, available for insertion into an incomplete germline VLR gene. Individual lymphocytes express a uniquely rearranged VLR gene in monoallelic fashion. Different evolutionary strategies were thus used to generate highly diverse lymphocyte receptors through rearrangement of LRR modules in agnathans (jawless fish) and of immunoglobulin gene segments in gnathostomes (jawed vertebrates). Adaptive immune responses in jawed vertebrates are initiated when antigens are recognized by specific lymphocyte receptors. Antigen receptor diversity is generated through recombination of variable, diversity and joining gene segments in the immunoglobulin and T-cell receptor (TCR) gene loci. This combinatorial rearrangement generates vast repertoires of antibodies against unprocessed anti- gens and of TCRs that recognize antigen fragments presented by major histocompatibility complex (MHC) class I and II molecules. Clonally diverse lymphocytes thus form the cornerstone of verte- brate adaptive immunity in the form of immunoglobulin-bearing B cells and TCR-bearing T cells that differentiate from stem-cell precursors within primary haematopoietic tissues and the thymus....
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pancer2004 - Somatic diversification of variable lymphocyte...

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