Since the TCR γ chain appears to be phylogenetically primitive [39] and the TCR γδ receptor shows intermediate binding properties [3], TCR γδ is a good candidate for the primordial receptor. It has also been speculated that hypermutation was a feature of the primitive receptor

[1, 40, 41], also because the AID gene is conserved in all vertebrates and was presumably present when the V-(D)-J rearrangement-based immune system originated. Some authors [1, 42] have indeed proposed that hypermutation is an ancient mechanism for generating diversity, perhaps preceding somatic rearrangement. Furthermore, the occurrence of somatic mutation in some invertebrates immune molecules has been reported [43, 44]. The discovery of marsupial and monotreme TRM [31, 45], shark Ku-0059436 nmr NAR-TcR [46], and camel heavy-chain antibodies [9] suggests that analogous atypical immune receptors might be found in other vertebrate lineages. Indeed, Staurosporine mw the ongoing extensive sequencing of the genomes of an ever-expanding

range of organisms is providing novel opportunities to analyze the genetics underlying evolution and adaptation in different mammalian lineages. On the other hand, as shown by the occurrence of TCRG somatic hypermutation in species as distantly related as the shark and the dromedary, comparative immunobiology of different vertebrate lineages can reveal ancient features of the immune systems and illustrate

a level of plasticity in TCR evolution heretofore unrealized. In conclusion, considering C. dromedarius as a “ruminant” we can make the following considerations: (i) requirements related to immunoprotective functions, including the first defensive barrier in the epithelia of the digestive tract, are likely to have induced in TCRG and TCRD loci of ruminants a sort of genome functional fluidity resulting in duplications of TCRG gene cassettes [5, 6] and in a marked expansion of the TCRDV1 multigene subgroup [7, 47]; as a consequence a large number of TCRGV and TCRDV genes, led to redundant recombinational events, which in turn produced transcripts with highly diversified variable domains; (ii) therefore it might be that in “ruminant” Adenosine triphosphate dromedary, TCR γδ evolution was favored by mutation in the productively rearranged TCRGV and TCRDV [14] genes, so that a large and diversified TCR γδ repertoire could be generated even in absence of functional reiterated genome duplications; (iii) tylopoda possess only three of the four cavities of the stomach of ruminants (they lack omasum) and occupy in the artiodactyl phylogeny a basal position compared with the other families belonging to the suborder “Ruminantia” (infraorder Pecora) [22, 48]. Then we can hypothesize that Camelidae by themselves might occupy a peculiar immunological niche.