title: Structural insights into the evolution of the adaptive immune system: the variable lymphocyte receptors of jawless vertebrates.
abstract: Adaptive immunity in jawless vertebrates is mediated by antigen receptors that are fundamentally different from those of jawed vertebrates. Whereas antibodies and T cell receptors (TCRs) are composed of immunoglobulin (Ig) domains, the variable lymphocyte receptors (VLRs) of jawless fish consist of leucine-rich repeat (LRR) modules. As with antibodies and TCRs, VLRs are assembled by DNA recombination in a process that generates a vast repertoire of receptors. VLRs recognize as diverse an array of particulate and soluble antigens as Ig-based antibodies, and do so with similar affinity and specificity. X-ray crystallographic studies of VLRs in complex with protein and carbohydrate antigens have shown that these LRR-based receptors use nearly all their concave surface to bind ligands, in addition to a highly variable loop in their C-terminal LRR capping module. This structural information, combined with a comprehensive analysis of VLR sequences, has revealed an almost perfect match between antigen-contacting positions and positions with highest sequence diversity. The independent evolution approximately 500 million years ago of LRR-based and Ig-based receptors of comparable diversity and antigen-binding properties provides evidence for the survival value of adaptive immunity in vertebrates.
authors.affiliation: University of Maryland Institute for Bioscience and Biotechnology Research, WM Keck Laboratory for Structural Biology, Rockville, MD 20850, USA. mariuzza@carb.nist.gov
authors.forename: Roy A
authors.initials: RA
authors.lastname: Mariuzza
authors.forename: C Alejandro
authors.initials: CA
authors.lastname: Velikovsky
authors.forename: Lu
authors.initials: L
authors.lastname: Deng
authors.forename: Gang
authors.initials: G
authors.lastname: Xu
authors.forename: Zeev
authors.initials: Z
authors.lastname: Pancer
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology*; D000818:Animals; D019143:Evolution, Molecular; D007107:Immune System / Q000276:immunology*; D007568:Jaw; D008214:Lymphocytes / Q000276:immunology*; D011487:Protein Conformation; D011971:Receptors, Immunologic / Q000276:immunology*; D014714:Vertebrates
chemical_list: D011971:Receptors, Immunologic