Characteristics of the somatic hypermutation in the Camelus dromedarius T cell receptor gamma (TRG) and delta (TRD) variable domains.

In previous reports, we had shown in Camelus dromedarius that diversity in T cell receptor gamma (TRG) 30 and delta (TRD) variable domains can be generated by somatic hypermutation (SHM). In the present 31 paper, we further the previous finding by analyzing 85 unique spleen cDNA sequences encoding a total 32 of 331 mutations from a single animal, and comparing the properties of the mutation profiles of drom- 33 edary TRG and TRD variable domains. The transition preference and the significant mutation frequency 34 in the AID motifs (dgyw/wrch and wa/tw) demonstrate a strong dependence of the enzymes mediating 35 SHM in TRG and TRD genes of dromedary similar to that of immunoglobulin genes in mammals. Overall, 36 results reveal no asymmetry in the motifs targeting, i.e. mutations are equally distributed among g:c and 37 a:t base pairs and replacement mutations are favored at the AID motifs, whereas neutral mutations 38 appear to be more prone to accumulate in bases outside of the motifs. A detailed analysis of clonal lin- 39 eages in TRG and TRD cDNA sequences also suggests that clonal expansion of mutated productive rear- 40 rangements may be crucial in shaping the somatic diversification in the dromedary. This is confirmed by 41 the fact that our structural models, computed by adopting a comparative procedure, are consistent with 42 the possibility that, irrespective of where (in the CDR-IMGT or in FR-IMGT) the diversity was generated 43 by mutations, both clonal expansion and selection seem to be strictly related to an enhanced structural 44 stability of the cd subunits.