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Dev Comp Immunol. 2014 Oct;46(2):300-13. doi: 10.1016/j.dci.2014.05.001. Epub 2014 May 13.

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

Author information

1
Department of Biology, University of Bari, via E. Orabona 4, 70125 Bari, Italy. Electronic address: salvatricemaria.ciccarese@uniba.it.
2
Department of Biology, University of Bari, via E. Orabona 4, 70125 Bari, Italy.
3
IMGT, Laboratoire d'ImmunoGénétique Moléculaire, Institut de Génétique Humaine, UPR CNRS 1142, Université Montpellier 2, 34396 Montpellier Cedex 5, France.
4
Biocomputing Group, CIRI-Health Science and Technologies/Department of Biology, University of Bologna, via Selmi 3, 40126 Bologna, Italy.
5
CNR, Institute for Biomedical Technologies of Bari, via Amendola, 70125 Bari, Italy.

Abstract

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

KEYWORDS:

Dromedary; IMGT; Somatic hypermutation; T cell receptor; TRG and TRD genes

PMID:
24836674
DOI:
10.1016/j.dci.2014.05.001
[Indexed for MEDLINE]

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