CD163/WC1 functions as pattern recognition receptors and co-receptors for the gamma delta TCR (68.17)

Abstract

Abstract γδ T cells are deemed critical to immune surveillance and protection since they are found as resident cells in many organs and tissues including in humans, cattle and mice. It is known that γδ T cells contribute to cellular immunity and protection against important pathogens, organizing granulomas in response to Mycobacteria and producing IFNγ following vaccination to Leptospira. However, it is not clear how best to engage γδ T cells and few efforts have directly addressed the contribution of co-receptor stimulation for doing so. We are filling this gap by addressing the hypothesis that the CD163/WC1 co-receptors on γδ T cells, as an example of PRRs on nonconventional T cells, can be exploited to fully activate these cells when combined with TCR activation. In this study, the complexity of the WC1 multi-gene family in cattle has been resolved. The WC1 family is composed of 13 genes with three structural forms whose sequences are conserved among individual cattle and breeds. These three structural forms have different intracytoplasmic tail sequences which require phosphorylation of distinct tyrosines for transmission of signaling through the TCR and lead to different functional outcomes. In addition, the specific activation of subpopulations of γδ T cells can be defined by the WC1 gene products expressed. The work will inform how PRR families might be exploited for efficacious vaccine design to activate nonconventional T cells that bridge innate and adaptive immune responses.