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, Ciro Leonardo Pierri
TL;DR
This study models the 3D structure of dromedary γδ T cell receptors and finds that CDR3 length affects how they bind to CD1D, similar to human NKT cells.
Contribution
The study reveals how TRD CDR3 length influences binding interactions in dromedary γδ T cells, linking them to CD1D-restricted NKT cells.
Findings
Long CDR3s in TRD are associated with CD1D-restricted γδ T cells in dromedaries.
Both V-gamma and V-delta domains interact with CD1D's G-alpha1-like and G-alpha2-like helices.
The findings highlight similarities between dromedary γδ T cells and human CD1D-restricted γδ NKT cells.
Abstract
Background: 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.…
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Taxonomy
TopicsT-cell and B-cell Immunology · Immune Cell Function and Interaction · Immunotherapy and Immune Responses