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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.

By a combination of rapid amplification of cDNA ends (RACE) and reverse transcription-polymerase chain reaction (RT-PCR) we identified three T cell receptor delta variable (TRDV) subgroups and five joining (TRDJ) genes expressed in spleen, tonsils and blood of Camelus dromedarius. We provide evidence that the high diversity in sequence and length of the third complementarity determining region (CDR3) is a major component of the TR delta chain variability. Moreover, the identification of the corresponding germline genes allowed us to find out for the first time in a mammalian organism that productively rearranged TRDV genes undergo somatic mutation: the mutation rate of the analysed TRDV4 region is 0.013 per base pair in spleen and 0.009 in blood. The point mutations are scattered throughout the length of the variable domain from framework region FR1 to FR4. This random distribution of the amino acid changes, instead of its CDR clustering observed in immunoglobulins (IG), indicates that somatic mutation in dromedary, while contributing to the development of the TRDV repertoire, is not under antigen selection. © 2011 Elsevier Ltd.