Department of Animal Science, Aarhus University, Blichers Allé 20, 8830, Tjele, Denmark.
GABI, INRA, AgroParisTech, Université Paris-Saclay, 78350, Jouy-en-Josas, France.
Mol Immunol. 2019 Oct;114:216-225. doi: 10.1016/j.molimm.2019.07.022. Epub 2019 Aug 3.
C-type lectin-like domain containing proteins (CTLDcps) mainly bind carbohydrate-based ligands, but also other ligands. CTLDcps are involved in several biological processes including cell adhesion, cell-cell interactions, and pathogen recognition. Pathogen recognition by myeloid cells, e.g. dendritic cells (DCs), can be facilitated through cell surface expressed CTLDcps. Cell surface expressed CTLDcps have been exploited in vaccine designs for specific targeting of human and mouse DCs using antibodies. In recent years, however, DC targeting using carbohydrate-based vaccines has gained interest due to low production cost, limited immunogenicity, and possibility of multivalent adjustment. In chicken, however, only a few CTLDcps have been identified. Identifying and annotating additional chicken CTLDcps (chCTLDcps) is needed to exploit carbohydrate-mediated DC targeting in chicken. Therefore, we searched the chicken GRCg6a assembly for novel chCTLDcps. We identified 28 chCTLDcps of which 10 had previously been described and also experimentally validated. RNA-seq and RT-qPCR confirmed mRNA expression of the remaining 18 identified chCTLDcps. A group of highly related chCTLDcps, moreover, was shown to be avian-specific and comprise novel members mapped to the proposed chicken natural killer gene complex. Two chCTLDcps, chCLEC17AL-A and chCLEC17AL-B, were found to share a recent common ancestor with CLEC17A. Putative mannose or fucose-binding sequence motifs, EPN and WND, were found in the CTLD of chCLEC17AL-A. Both contained intracellular internalisation and signalling sequence motifs. In conclusion, several chCTLDcps were identified and their expression confirmed. Both chCLEC17AL-A and -B showed promise as potential targets in carbohydrate-based chicken vaccine strategies. Determination of DC-specific expression of chCLEC17AL-A and -B, thus, might prove useful in chicken vaccinology.
C 型凝集素样结构域蛋白 (CTLDcps) 主要结合基于碳水化合物的配体,但也结合其他配体。CTLDcps 参与多种生物学过程,包括细胞黏附、细胞-细胞相互作用和病原体识别。髓样细胞(例如树突状细胞 (DCs))通过细胞表面表达的 CTLDcps 促进病原体识别。已经利用细胞表面表达的 CTLDcps 设计了针对人类和小鼠 DCs 的抗体特异性靶向的疫苗。然而,近年来,由于生产成本低、免疫原性有限以及多价调整的可能性,基于碳水化合物的疫苗靶向 DC 引起了关注。然而,在鸡中,只有少数 CTLDcps 被鉴定出来。需要鉴定和注释额外的鸡 CTLDcps(chCTLDcps),以利用鸡中碳水化合物介导的 DC 靶向作用。因此,我们在鸡 GRCg6a 组装中搜索新的 chCTLDcps。我们鉴定了 28 个 chCTLDcps,其中 10 个以前已被描述并进行了实验验证。RNA-seq 和 RT-qPCR 证实了其余 18 个鉴定出的 chCTLDcps 的 mRNA 表达。此外,一组高度相关的 chCTLDcps 被证明是禽特异性的,并且包含映射到拟议的鸡自然杀伤基因复合物的新型成员。两个 chCTLDcps,chCLEC17AL-A 和 chCLEC17AL-B,与 CLEC17A 具有最近的共同祖先。在 chCLEC17AL-A 的 CTLD 中发现了假定的甘露糖或岩藻糖结合序列基序 EPN 和 WND。两者都包含细胞内内化和信号转导序列基序。总之,鉴定了多个 chCTLDcps 并证实了它们的表达。chCLEC17AL-A 和 -B 都有可能成为基于碳水化合物的鸡疫苗策略的潜在靶点。因此,chCLEC17AL-A 和 -B 的 DC 特异性表达的确定可能对鸡疫苗学有用。