Structures of human γδ T cell receptor-CD3 complex.

Gamma delta (γδ) T cells, a unique T cell subgroup, are crucial in various immune responses and immunopathology1-3. The γδ T cell receptor (TCR), generated by γδ T cells, recognizes a diverse range of antigens independently of the major histocompatibility complex2. The γδ TCR associates with CD3 subunits, initiating T cell activation and holding great potential in immunotherapy4. Here, we report the structures of two prototypical human Vγ9Vδ2 and Vγ5Vδ1 TCR-CD3 complexes5,6, unveiling two distinct assembly mechanisms that depend on Vγ usage. The Vγ9Vδ2 TCR-CD3 complex is monomeric, with considerable conformational flexibility in the TCRγ/TCRδ extracellular domain (ECD) and connecting peptides (CPs). The length of CPs regulates the ligand association and T cell activation. Additionally, a cholesterol-like molecule wedges into the transmembrane region, exerting an inhibitory role in TCR signaling. The Vγ5Vδ1 TCR-CD3 complex displays a dimeric architecture, where two protomers nestle back-to-back via their Vγ5 domains of TCR ECDs. Our biochemical and biophysical assays further corroborate the dimeric structure. Importantly, the dimeric form of the Vγ5Vδ1 TCR is essential for T cell activation. These findings reveal organizing principles of the γδ TCR-CD3 complex, providing insights into the γδ TCR unique properties and facilitating immunotherapeutic interventions.

Multiple genotypes infection and molecular characterization of Torque teno neovison virus: A novel Anelloviridae of mink in China.

A novel Torque teno neovison virus (TTVs) was identified in specimens collected from dead mink during an outbreak of the Aleutian mink disease virus. Eighteen complete genomic sequences were obtained, ranging from 2109 to 2158 nucleotides in length and consisting of an untranslated region and three open reading frames. The genomic organization of mink TTVs is similar to previously reported anelloviruses. However, the deduced amino acid sequence of its ORF1 protein shows genetic diversity compared to related anelloviruses, suggesting that it represents a putative new species within the Anelloviridae family. This study provides a detailed molecular characterization of the novel mink anelloviruses, including its codon usage pattern, origin, and evolution. Analysis of the viral genomic sequences reveals the existence of multiple genotypes of co-infection. Principal component analysis and phylogenetic trees confirm the coexistence of multiple genotypes. Furthermore, the codon usage analyses indicate that mink TTVs have a genotype-specific codon usage pattern and show a low codon usage bias. Host-specific adaptation analysis suggests that TTVs are less adapted to mink. The possible origin and evolutionary history of mink TTVs were elucidated. Mink TTVs was genetically closely related to giant panda anellovirus, representing a new species. The observed incongruence between the phylogenetic history of TTVs and that of their hosts suggests that the evolution of anellovirus is largely determined by cross-species transmission. The study provides insights into the co-infection and genetic evolution of anellovirus in China.

Detection, genetic, and codon usage bias analyses of the VP2 gene of mink bocavirus.

Mink bocavirus 1 (MiBoV1), a novel virus detected from the feces of domestic minks in China in 2016, may be related to gastrointestinal diseases. However, its prevalence and genetic characteristics are poorly described. In this study, we examined 192 samples collected from minks in the major mink industry province from northern China. PCR results showed that 10 samples (5.2%) were positive for MiBoV1, and 60% of MiBoV1-positive samples were co-infected with Aleutian mink disease virus or mink circovirus. MiBoV1 was detected in six serum samples. Sequence analysis demonstrated that the VP2 gene of MiBoV1 was highly conserved and had low viral diversity over the VP2 region and unique nucleotide mutations. Phylogenetic analysis of the VP2 sequence demonstrated that MiBoV1 strains formed two clades and were grouped with California sea lion bocavirus, Canine bocavirus, and Feline bocavirus. Codon usage analysis revealed that most of the preferentially used codons in MiBoV1 were A- or U-ended codons, and no evident codon usage bias was found. This study provides evidence that MiBoV1 has a low prevalence in Jilin and Hebei provinces in China. Moreover, it contributes information regarding the expansion of the limited mink bocavirus sequence and determines the codon usage bias of the VP2 gene for the first time. Epidemiological surveillance is necessary to understand the importance and evolution of MiBoV1.