Structural analysis of the nurse shark (new) antigen receptor (NAR): molecular convergence of NAR and unusual mammalian immunoglobulins.

نویسندگان

  • K H Roux
  • A S Greenberg
  • L Greene
  • L Strelets
  • D Avila
  • E C McKinney
  • M F Flajnik
چکیده

We recently have identified an antigen receptor in sharks called NAR (new or nurse shark antigen receptor) that is secreted by splenocytes but does not associate with Ig light (L) chains. The NAR variable (V) region undergoes high levels of somatic mutation and is equally divergent from both Ig and T cell receptors (TCR). Here we show by electron microscopy that NAR V regions, unlike those of conventional Ig and TCR, do not form dimers but rather are independent, flexible domains. This unusual feature is analogous to bona fide camelid IgG in which modifications of Ig heavy chain V (VH) sequences prevent dimer formation with L chains. NAR also displays a uniquely flexible constant (C) region. Sequence analysis and modeling show that there are only two types of expressed NAR genes, each having different combinations of noncanonical cysteine (Cys) residues in the V domains that likely form disulfide bonds to stabilize the single antigen-recognition unit. In one NAR class, rearrangement events result in mature genes encoding an even number of Cys (two or four) in complementarity-determining region 3 (CDR3), which is analogous to Cys codon expression in an unusual human diversity (D) segment family. The NAR CDR3 Cys generally are encoded by preferred reading frames of rearranging D segments, providing a clear design for use of preferred reading frame in antigen receptor D regions. These unusual characteristics shared by NAR and unconventional mammalian Ig are most likely the result of convergent evolution at the molecular level.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Somatic hypermutation of the new antigen receptor gene (NAR) in the nurse shark does not generate the repertoire: possible role in antigen-driven reactions in the absence of germinal centers.

The new antigen receptor (NAR) gene in the nurse shark diversifies extensively by somatic hypermutation. It is not known, however, whether NAR somatic hypermutation generates the primary repertoire (like in the sheep) or rather is used in antigen-driven immune responses. To address this issue, the sequences of NAR transmembrane (Tm) and secretory (Sec) forms, presumed to represent the primary a...

متن کامل

Commentary In an immunological twilight zone

Early in their evolution, perhaps during their transition from Agnatha (jawless fish) to Gnathostomata (jawed animals), vertebrates committed as much as 1% of their proteinencoding genome to a new system of defense against parasites (1). Central to this anticipatory (adaptive) immune system (2) are three types of antigen receptor—immunoglobulin (Ig), T cell receptor (Tcr), and major histocompat...

متن کامل

- Cell receptors

Sharks possess the four canonical T-cell receptor (TCR) chains known from other vertebrates: α, β, γ, and δ. The loci encoding these chains employ recombination-activating gene (RAG)mediated somatic cell V(D)J rearrangement mechanisms for diverse repertoires. Sharks have some additional immunogenetic TCR capacity, including the doubly rearranging NAR-TCR δ, somatic hypermutation, and trans-rear...

متن کامل

Isolation of anti-toxin single domain antibodies from a semi-synthetic spiny dogfish shark display library

BACKGROUND Shark heavy chain antibody, also called new antigen receptor (NAR), consists of one single Variable domain (VH), containing only two complementarity-determining regions (CDRs). The antigen binding affinity and specificity are mainly determined by these two CDRs. The good solubility, excellent thermal stability and complex sequence variation of small single domain antibodies (sdAbs) m...

متن کامل

An evolutionarily mobile antigen receptor variable region gene: doubly rearranging NAR-TcR genes in sharks.

Distinctive Ig and T cell receptor (TcR) chains define the two major lineages of vertebrate lymphocyte yet similarly recognize antigen with a single, membrane-distal variable (V) domain. Here we describe the first antigen receptor chain that employs two V domains, which are generated by separate VDJ gene rearrangement events. These molecules have specialized "supportive" TcRdeltaV domains membr...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:
  • Proceedings of the National Academy of Sciences of the United States of America

دوره 95 20  شماره 

صفحات  -

تاریخ انتشار 1998