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


ABSTRACT: 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 membrane-proximal to domains with most similarity to IgNAR V. The ancestral NAR V gene encoding this domain is hypothesized to have recombined with the TRD locus in a cartilaginous fish ancestor >200 million years ago and encodes the first V domain shown to be used in both Igs and TcRs. Furthermore, these data support the view that gamma/delta TcRs have for long used structural conformations recognizing free antigen.

SUBMITTER: Criscitiello MF 

PROVIDER: S-EPMC1458790 | biostudies-literature | 2006 Mar

REPOSITORIES: biostudies-literature

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

Criscitiello Michael F MF   Saltis Mark M   Flajnik Martin F MF  

Proceedings of the National Academy of Sciences of the United States of America 20060320 13


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 membrane-proximal to domains with most similarity to IgNAR V. The ancestral NAR V gene encoding this domain  ...[more]

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