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Three-dimensional modeling of Camelus dromedarius T cell receptor Gamma (TRG)_Delta (TRD)/CD1D complex reveals different binding interactions depending on the TRD CDR3 length
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Three-dimensional modeling of Camelus dromedarius T cell receptor Gamma (TRG)_Delta (TRD)/CD1D complex reveals different binding interactions depending on the TRD CDR3 length

Salvatrice Ciccarese, Marie-Paule Lefranc, Giulia C M Perrone, Pietro D’addabbo et Ciro Leonardo Pierri
Antibodies, Vol.14(2)
2025
PMCID: PMC12189835
PMID: 40558100

Résumé

3D modeling protein-protein interaction multiple sequence alignments (MSA) TRG and TRD loci T cell receptor IMGT unique numbering Camelus dromedarius
In the adaptive immune response of the dromedary (Camelus dromedarius, Camdro), the T cell receptor (TR) repertoire of the gamma–delta (γδ) T cells is unusually diversified both by somatic hypermutation in rearranged TR gamma (TRG) and delta (TRD) genes and by the diversity in sequence and length of the third complementarity-determining region (CDR3) of the TRD chain. Methods: the purpose was to investigate, in the absence of 3D structures, the role of Camdro γδ T cells, focusing on the binding interactions at the interface between the V-gamma and V-delta domains, and in complex with the CD1D, a major histocompatibily class I (MH1)-like glycoprotein presenting lipid antigen in association with B2M. A combination of hypermutated TRG dromedary cDNA clones was paired with TRD clones bearing very long, long, or short CDR3s, all isolated from the spleen of a single animal. Results: the 3D models of the Camdro TRG_TRD/CD1D_B2M complexes were inferred using the Homo sapiens 3D structure and the ImMunoGeneTics (IMGT) numbering for V, C, and G domains, and investigated for binding interactions at the interface of the paired V-gamma_V-delta and at the interface with CD1D. Our results suggest that transcripts with long CDR3s may derive from a population of CD1D-restricted γδ T cells. Both the CD1D G-alpha1-like and G-alpha-2 like domain helices were contacted by both the V-gamma and V-delta CDR-IMGT loops. Conclusions: our findings further emphasize the similarity between the γδ T cells population we analyzed in Camelus dromedarius and the CD1D-restricted γδ NKT cells in Homo sapiens.

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