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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2025-05-01
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| author | Salvatrice Ciccarese Marie-Paule Lefranc Giulia C. M. Perrone Pietro D’Addabbo Ciro Leonardo Pierri |
| author_facet | Salvatrice Ciccarese Marie-Paule Lefranc Giulia C. M. Perrone Pietro D’Addabbo Ciro Leonardo Pierri |
| author_sort | Salvatrice Ciccarese |
| collection | DOAJ |
| description | 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>. |
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| issn | 2073-4468 |
| language | English |
| publishDate | 2025-05-01 |
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| spelling | doaj-art-8e61d1f5b46a41b9a4c4585d41f75efe2025-08-20T02:24:22ZengMDPI AGAntibodies2073-44682025-05-011424610.3390/antib14020046Three-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 LengthSalvatrice Ciccarese0Marie-Paule Lefranc1Giulia C. M. Perrone2Pietro D’Addabbo3Ciro Leonardo Pierri4Department of Biosciences, Biotechnologies and Environment, University of Bari Aldo Moro, Via E.Orabona, 4-70125 Bari, ItalyIMGT<sup>®</sup>, the International ImMunoGeneTics Information System<sup>®</sup> (IMGT), Laboratoire d’ImmunoGénétique Moléculaire (LIGM), Institut de Génétique Humaine (IGH), Centre National de la Recherche Scientifique (CNRS), Université de Montpellier (UM), 34090 Montpellier, FranceLaboratory of Biochemistry, Structural, and Molecular Biology, Department of Pharmacy—Pharmaceutical Sciences, University of Bari, Via E. Orabona, 4-70125 Bari, ItalyDepartment of Biosciences, Biotechnologies and Environment, University of Bari Aldo Moro, Via E.Orabona, 4-70125 Bari, ItalyLaboratory of Biochemistry, Structural, and Molecular Biology, Department of Pharmacy—Pharmaceutical Sciences, University of Bari, Via E. Orabona, 4-70125 Bari, ItalyBackground: 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>.https://www.mdpi.com/2073-4468/14/2/46T cell receptor<i>Camelus dromedarius</i>TRG and TRD locimultiple sequence alignments (MSA)3D modelingprotein–protein interaction |
| spellingShingle | Salvatrice Ciccarese Marie-Paule Lefranc Giulia C. M. Perrone Pietro D’Addabbo Ciro Leonardo Pierri 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 Antibodies T cell receptor <i>Camelus dromedarius</i> TRG and TRD loci multiple sequence alignments (MSA) 3D modeling protein–protein interaction |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | T cell receptor <i>Camelus dromedarius</i> TRG and TRD loci multiple sequence alignments (MSA) 3D modeling protein–protein interaction |
| url | https://www.mdpi.com/2073-4468/14/2/46 |
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