Identification and tissue-expression profiling of novel chicken c-type lectin-like domain containing proteins as potential targets for carbohydrate-based vaccine strategies

Abstract

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.

Keywords: C-type lectin-like domain; Chicken; Chicken NKC; Containing proteins; Pattern-Recognition receptors; Vaccine design.