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T细胞受体γ(TRG)-δ(TRD)/CD1D复合物的三维建模揭示了取决于TRD互补决定区3(CDR3)长度的不同结合相互作用。

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

作者信息

Ciccarese Salvatrice, Lefranc Marie-Paule, Perrone Giulia C M, D'Addabbo Pietro, Pierri Ciro Leonardo

机构信息

Department of Biosciences, Biotechnologies and Environment, University of Bari Aldo Moro, Via E.Orabona, 4-70125 Bari, Italy.

IMGT®, the International ImMunoGeneTics Information System® (IMGT), Laboratoire d'ImmunoGénétique Moléculaire (LIGM), Institut de Génétique Humaine (IGH), Centre National de la Recherche Scientifique (CNRS), Université de Montpellier (UM), 34090 Montpellier, France.

出版信息

Antibodies (Basel). 2025 May 29;14(2):46. doi: 10.3390/antib14020046.

Abstract

BACKGROUND

In the adaptive immune response of the dromedary (, 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 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 and the CD1D-restricted γδ NKT cells in .

摘要

背景

在单峰驼(Camelus dromedarius)的适应性免疫反应中,γδ T细胞的T细胞受体(TR)库异常多样化,这既源于重排的TRγ(TRG)和δ(TRD)基因中的体细胞超突变,也源于TRD链第三个互补决定区(CDR3)的序列和长度多样性。

方法

目的是在缺乏三维结构的情况下,研究单峰驼γδ T细胞的作用,重点关注V-γ和V-δ结构域之间界面处的结合相互作用,以及与CD1D(一种与B2M结合呈递脂质抗原的主要组织相容性I类(MH1)样糖蛋白)形成的复合物。将超突变的TRG单峰驼cDNA克隆与携带非常长、长或短CDR3的TRD克隆配对,所有这些克隆均从一只动物的脾脏中分离得到。

结果

利用V、C和G结构域的三维结构和免疫遗传学(IMGT)编号推断出单峰驼TRG_TRD/CD1D_B2M复合物的三维模型,并研究了配对的V-γ_V-δ界面处以及与CD1D界面处的结合相互作用。我们的结果表明,具有长CDR3的转录本可能来源于一群受CD1D限制的γδ T细胞。V-γ和V-δ CDR-IMGT环均与CD1D的G-α1样和G-α2样结构域螺旋接触。

结论

我们的研究结果进一步强调了我们在本研究中分析的γδ T细胞群体与文献[具体文献未提及]中受CD1D限制的γδ NKT细胞之间的相似性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5263/12189835/47f2eefa7ddb/antibodies-14-00046-g001.jpg

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