# 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

## 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.

## Key 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. 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.