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The phylogenetic origins of the antigen-binding receptors and somatic diversification mechanisms

Authors

  • John P. Cannon,

    1. Department of Molecular Genetics, All Children's Hospital, St. Petersburg, FL, USA.
    2. H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
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  • Robert N. Haire,

    1. Department of Pediatrics, University of South Florida College of Medicine, Children's Research Institute, St. Petersburg, FL, USA.
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  • Jonathan P. Rast,

    1. Sunnybrook and Women's College, Health Sciences Center, Toronto, Ontario, Canada.
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  • Gary W. Litman

    Corresponding author
    1. Department of Molecular Genetics, All Children's Hospital, St. Petersburg, FL, USA.
    2. H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
    3. Department of Pediatrics, University of South Florida College of Medicine, Children's Research Institute, St. Petersburg, FL, USA.
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* Gary W Litman
Department of Pediatrics
University of South Florida College of Medicine
Children's Research Institute
830 First Street South
St. Petersburg, FL 33701
USA
Tel.: +1 727 553 3601
Fax: +1 727 553 3610
E-mail: litmang@allkids.org

Abstract

Summary:  The adaptive immune system arose in ancestors of the jawed vertebrates approximately 500 million years ago. Homologs of immunoglobulins (Igs), T-cell antigen receptors (TCRs), major histocompatibility complex I (MHC I) and MHC II, and the recombination-activating genes (RAGs) have been identified in all extant classes of jawed vertebrates; however, no definitive homolog of any of these genes has been identified in jawless vertebrates or invertebrates. RAG-mediated recombination and associated junctional diversification of both Ig and TCR genes occurs in all jawed vertebrates. In the case of Igs, somatic variation is expanded further through class switching, gene conversion, and somatic hypermutation. Although the identity of the ‘primordial’ receptor that was interrupted by the recombination mechanism in jawed vertebrates may never be established, many different families of genes that exhibit predicted characteristics of such a receptor have been described both within and outside the jawed vertebrates. Recent data from various model systems point toward a continuum of immune receptor diversity, encompassing many different families of recognition molecules whose functions are integrated in an organism's response to pathogenic invasion. Various approaches, including both genomic and protein-functional analyses, currently are being applied in jawless vertebrates, protochordates, and other invertebrate deuterostome systems and may yield definitive evidence regarding the presence or absence of adaptive immune homologs in species lacking adaptive immune systems. Such studies have the potential for uncovering previously unknown mechanisms of generating receptor diversity.

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