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 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.
Department of Microbiology and Immunology, University of Maryland, Howard Hall, Suite 324, 660 West Redwood Street, Baltimore, MD 21201-1559, USA.
Michael F
MF
Criscitiello
Mark
M
Saltis
Martin F
MF
Flajnik
D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D019143:Evolution, Molecular; D005786:Gene Expression Regulation; D015321:Gene Rearrangement / Q000235:genetics* / Q000276:immunology; D014644:Genetic Variation / Q000235:genetics*; D016678:Genome / Q000235:genetics; D006801:Humans; D008221:Lymphoid Tissue / Q000378:metabolism; D008969:Molecular Sequence Data; D009928:Organ Specificity; D010802:Phylogeny; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000737:chemistry / Q000145:classification / Q000276:immunology* / Q000378:metabolism*; D016415:Sequence Alignment; D012754:Sharks / Q000235:genetics* / Q000276:immunology*
D016692:Receptors, Antigen, T-Cell, gamma-delta