Three-Dimensional Modeling of <i>Camelus dromedarius</i> T Cell Receptor Gamma (TRG)_Delta (TRD)/CD1D Complex Reveals Different Binding Interactions Depending on the TRD CDR3 Length

Background: In the adaptive immune response of the dromedary (<i>Camelus dromedarius</i>, 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 dive...

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Main Authors: Salvatrice Ciccarese, Marie-Paule Lefranc, Giulia C. M. Perrone, Pietro D’Addabbo, Ciro Leonardo Pierri
Format: Article
Language:English
Published: MDPI AG 2025-05-01
Series:Antibodies
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Online Access:https://www.mdpi.com/2073-4468/14/2/46
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Summary:Background: In the adaptive immune response of the dromedary (<i>Camelus dromedarius</i>, 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 <i>Homo sapiens</i> 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 <i>Camelus dromedarius</i> and the CD1D-restricted γδ NKT cells in <i>Homo sapiens</i>.
ISSN:2073-4468