title: A new high molecular weight immunoglobulin class from the carcharhine shark: implications for the properties of the primordial immunoglobulin.
abstract: All immunoglobulins and T-cell receptors throughout phylogeny share regions of highly conserved amino acid sequence. To identify possible primitive immunoglobulins and immunoglobulin-like molecules, we utilized 3' RACE (rapid amplification of cDNA ends) and a highly conserved constant region consensus amino acid sequence to isolate a new immunoglobulin class from the sandbar shark Carcharhinus plumbeus. The immunoglobulin, termed IgW, in its secreted form consists of 782 amino acids and is expressed in both the thymus and the spleen. The molecule overall most closely resembles mu chains of the skate and human and a new putative antigen binding molecule isolated from the nurse shark (NAR). The full-length IgW chain has a variable region resembling human and shark heavy-chain (VH) sequences and a novel joining segment containing the WGXGT motif characteristic of H chains. However, unlike any other H-chain-type molecule, it contains six constant (C) domains. The first C domain contains the cysteine residue characteristic of C mu1 that would allow dimerization with a light (L) chain. The fourth and sixth domains also contain comparable cysteines that would enable dimerization with other H chains or homodimerization. Comparison of the sequences of IgW V and C domains shows homology greater than that found in comparisons among VH and C mu or VL, or CL thereby suggesting that IgW may retain features of the primordial immunoglobulin in evolution.
authors.affiliation: University of Arizona, Department of Microbiology and Immunology, College of Medicine, Tucson, 85724, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Berstein
authors.forename: S F
authors.initials: SF
authors.lastname: Schluter
authors.forename: S
authors.initials: S
authors.lastname: Shen
authors.forename: J J
authors.initials: JJ
authors.lastname: Marchalonis
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D005075:Biological Evolution; D003001:Cloning, Molecular; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D005803:Genes, Immunoglobulin; D006801:Humans; D007127:Immunoglobulin Constant Regions / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007136:Immunoglobulins / Q000737:chemistry* / Q000145:classification / Q000235:genetics*; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010802:Phylogeny; D017386:Sequence Homology, Amino Acid; D012754:Sharks / Q000235:genetics* / Q000276:immunology*
chemical_list: D017931:DNA Primers; D018076:DNA, Complementary; D007127:Immunoglobulin Constant Regions; D007135:Immunoglobulin Variable Region; D007136:Immunoglobulins