Four primordial immunoglobulin light chain isotypes, including λ and κ, identified in the most primitive living jawed vertebrates

Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
European Journal of Immunology (Impact Factor: 4.52). 11/2007; 37(10):2683-94. DOI: 10.1002/eji.200737263
Source: PubMed

ABSTRACT The discovery of a fourth immunoglobulin (Ig) light (L) chain isotype in sharks has revealed the origins and natural history of all vertebrate L chains. Phylogenetic comparisons have established orthology between this new shark L chain and the unique Xenopus L chain isotype sigma. More importantly, inclusion of this new L chain family in phylogenetic analyses showed that all vertebrate L chains can be categorized into four ancestral clans originating prior to the emergence of cartilaginous fish: one restricted to elasmobranchs (sigma-cart/type I), one found in all cold-blooded vertebrates (sigma/teleost type 2/elasmobranch type IV), one in all groups except bony fish (lambda/elasmobranch type II), and one in all groups except birds (kappa/elasmobranch type III/teleost type 1 and 3). All four of these primordial L chain isotypes (sigma, sigma-cart, lambda and kappa) have maintained separate V region identities since their emergence at least 450 million years ago, suggestive of an ancient physiological distinction of the L chains. We suggest that, based upon unique, discrete sizes of complementarity determining regions 1 and 2 and other features of the V region sequences, the different L chain isotypes arose to provide different functional conformations in the Ig binding site when they pair with heavy chains.

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Available from: Mike Criscitiello, Sep 29, 2014
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    • "A close examination of V L based on its phylogenetic relationships , CDR lengths and RSS orientation , recognized four ancestral V L clades that were maintained throughout the vertebrates ( Criscitiello and Flajnik , 2007 ) . A distinct variant of the s isotype , which was named s‐cart ( for cartilaginous fish ) , has been identified only in the shark ( Criscitiello and Flajnik , 2007 ) . The organization of the light chain loci among the vertebrates is not as definitive or diagnostic as for the heavy chain loci and can consist of cluster‐type , translocon‐type or perhaps other variations ( Hsu and Criscitiello , 2006 ) . "
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    ABSTRACT: We have analyzed the available genome and transcriptome resources from the coelacanth in order to characterize genes involved in adaptive immunity. Two highly distinctive IgW-encoding loci have been identified that exhibit a unique genomic organization, including a multiplicity of tandemly repeated constant region exons. The overall organization of the IgW loci precludes typical heavy chain class switching. A locus encoding IgM could not be identified either computationally or by using several different experimental strategies. Four distinct sets of genes encoding Ig light chains were identified. This includes a variant sigma-type Ig light chain previously identified only in cartilaginous fishes and which is now provisionally denoted sigma-2. Genes encoding α/β and γ/δ T-cell receptors, and CD3, CD4, and CD8 co-receptors also were characterized. Ig heavy chain variable region genes and TCR components are interspersed within the TCR α/δ locus; this organization previously was reported only in tetrapods and raises questions regarding evolution and functional cooption of genes encoding variable regions. The composition, organization and syntenic conservation of the major histocompatibility complex locus have been characterized. We also identified large numbers of genes encoding cytokines and their receptors, and other genes associated with adaptive immunity. In terms of sequence identity and organization, the adaptive immune genes of the coelacanth more closely resemble orthologous genes in tetrapods than those in teleost fishes, consistent with current phylogenomic interpretations. Overall, the work reported described herein highlights the complexity inherent in the coelacanth genome and provides a rich catalog of immune genes for future investigations. J. Exp. Zool. (Mol. Dev. Evol.) 9999B: 1-26, 2014. © 2014 Wiley Periodicals, Inc.
    Journal of Experimental Zoology Part B Molecular and Developmental Evolution 09/2014; 322(6). DOI:10.1002/jez.b.22558 · 1.88 Impact Factor
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    • "The emerging classification system currently differentiates between four ancestral clans: kappa (κ/elasmobranch type III/NS4/ Teleost L1, L3, F, G/Xenopus r), lambda (λ/elasmobranch type II), sigma (σ/teleost L2/ elasmobranch type IV), and sigma cart (σ-cart). Criscitiello and Flajnik (2007) have proposed an IgL classification system based on criteria of sequence homology, and the spacing of heptamer and nonamers of recombination signal sequences (RSS). In addition, the genomic configuration of IgL gene segments and the length of the complementary determining regions (CDR) of corresponding V L gene segments support a syntenic approach to IgL classification. "
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    ABSTRACT: The gene segments encoding antibodies have been studied in many capacities and represent some of the best-characterized gene families in traditional animal disease models (mice and humans). To date, multiple immunoglobulin light chain (IgL) isotypes have been found in vertebrates and it is unclear as to which isotypes might be more primordial in nature. Sequence data emerging from an array of fish genome projects is a valuable resource for discerning complex multigene assemblages in this critical branch point of vertebrate phylogeny. Herein, we have analyzed the genomic organization of medaka (Oryzias latipes) IgL gene segments based on recently released genome data. The medaka IgL locus located on chromosome 11 contains at least three clusters of IgL gene segments comprised of multiple gene assemblages of the kappa light chain isotype. These data suggest that medaka IgL gene segments may undergo both intra- and inter-cluster rearrangements as a means to generate additional diversity. Alignments of expressed sequence tags to concordant gene segments which revealed each of the three IgL clusters are expressed. Collectively, these data provide a genomic framework for IgL genes in medaka and indicate that Ig diversity in this species is achieved from at least three distinct chromosomal regions.
    Immunogenetics 02/2013; 65(5). DOI:10.1007/s00251-013-0678-9 · 2.49 Impact Factor
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    • "RSS orientation and CDR1/CDR2 lengths; based upon these features 116 it has been suggested that the different isotypes emerged over 117 450 MYA, and have been maintained to provide different bind- 118 ing-site structures upon heavy chain pairing (Criscitiello and Flaj- 119 nik, 2007). "
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    ABSTRACT: The cartilaginous fish (chimeras, sharks, skates and rays) are the oldest group relative to mammals in which an adaptive immune system founded upon immunoglobulins has been found. In this manuscript we characterize the immunoglobulins of the spiny dogfish (Squalus acanthias) at both the molecular and expressed protein levels. Despite the presence of hundreds of IgM clusters in this species the serum levels of this isotype are comparatively low. However, analysis of cDNA sequences and serum protein suggests microheterogeneity in the IgM heavy chains and supports the proposal that different clusters are preferentially used in the two forms (monomer or pentamer) of this isotype. We also found that the IgNAR isotype in this species exists in a previously unknown multimeric format in serum. Finally, we identified a new form of the IgW isotype (the shark IgD orthologue), in which the leader is spliced directly to the first constant domain, resulting in a molecule lacking an antigen-binding domain.
    Developmental and comparative immunology 04/2012; 36(4):665-79. DOI:10.1016/j.dci.2011.10.007 · 3.71 Impact Factor
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