title: Generation of diversity by somatic mutation in the Camelus dromedarius T-cell receptor gamma variable domains.
abstract: In jawed vertebrates the V-(D)-J rearrangement is the main mechanism generating limitless variations of antigen-specific receptors, immunoglobulins (IGs), and T-cell receptors (TCRs) from few genes. Once the initial diversity is established in primary lymphoid organs, further diversification occurs in IGs by somatic hypermutation, a mechanism from which rearranged TCR genes were thought to be excluded. Here, we report the locus organization and expression of the T-cell receptor gamma (TCRG) genes in the Arabian camel (Camelus dromedarius). Expression data provide evidence that dromedary utilizes only two TCRG V-J genomic arrangements and, as expected, CDR3 contributes the major variability in the V domain. The data also suggest that diversity might be generated by mutation in the productively rearranged TCRGV genes. As for IG genes, the mutational target is biased toward G and C bases and (A/G/T)G(C/T)(A/T) motif (or DGYW). The replacement and synonymous substitutions (R/S) ratios in TCRGV regions are higher for CDR than for framework region, thus suggesting selection toward amino acid changes in CDR. Using the counterpart human TCR γδ receptor as a template, structural models computed adopting a comparative procedure show that nonconservative mutations contribute to diversity in CDR2 and at the γδ V domain interface.
authors.affiliation: Department of Biology, University of Bari, Bari, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Vaccarelli
authors.forename: Rachele
authors.initials: R
authors.lastname: Antonacci
authors.forename: Gianluca
authors.initials: G
authors.lastname: Tasco
authors.forename: Fengtang
authors.initials: F
authors.lastname: Yang
authors.forename: Luca
authors.initials: L
authors.lastname: Giordano
authors.forename: Hassan M
authors.initials: HM
authors.lastname: El Ashmaoui
authors.forename: Mohamed S
authors.initials: MS
authors.lastname: Hassanane
authors.forename: Serafina
authors.initials: S
authors.lastname: Massari
authors.forename: Rita
authors.initials: R
authors.lastname: Casadio
authors.forename: Salvatrice
authors.initials: S
authors.lastname: Ciccarese
mesh_terms: D000818:Animals; D002162:Camelus / Q000235:genetics / Q000276:immunology*; D022801:Complementarity Determining Regions / Q000235:genetics / Q000276:immunology*; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor / Q000502:physiology*; D019675:Genes, T-Cell Receptor gamma / Q000502:physiology*; D006801:Humans
chemical_list: D022801:Complementarity Determining Regions