Abstract
γδ T cells have broad reactivity and actively participate in protective immunity against tumors and infectious disease-causing organisms. In γδ-high species such as ruminants and other artiodactyls many γδ T cells bear the lineage-specific markers known as WC1. WC1 molecules are scavenger receptors coded for by a multigenic array and are closely related to SCART found on murine γδ T cells and CD163 found on a variety of cells. We have previously shown that WC1 molecules are hybrid pattern recognition receptors thereby binding pathogens as well as signaling co-receptors for the γδ T cell receptor. WC1+ γδ T cells can be divided into two major subpopulations differentiated by the WC1 genes they express and the pathogens to which they respond. Therefore, we hypothesize that optimal γδ T cell responses are contingent on pathogen binding to WC1 molecules, especially since we have shown that silencing WC1 results in an inability of γδ T cells from primed animals to respond to the pathogen Leptospira, a model system we have employed extensively. Despite this knowledge about the crucial role WC1 plays in γδ T cell biology, the pattern of WC1 gene expression by individual γδ T cells was not known but is critical to devise methods to engage γδ T cells for responses to specific pathogens. To address this gap, we generated 78 γδ T cell clones. qRT-PCR evaluation showed that approximately 75% of the clones had one to three WC1 genes transcribed but up to six per cell occurred. The co-transcription of WC1 genes by clones showed many combinations and some WC1 genes were transcribed by both subpopulations although there were differences in the overall pattern of WC1 genes transcription. Despite this overlap, Leptospira-responsive WC1+ memory γδ T cell clones were shown to have a significantly higher propensity to express WC1 molecules that are known to bind to the pathogen.
Highlights
WC1 family members are T cell co-receptors and pathogen recognition receptors uniquely expressed by the majority of γδ T cells in the blood of ruminants [1]
We have previously shown that WC1 molecules are hybrid pattern recognition receptors thereby binding pathogens as well as signaling co-receptors for the γδ T cell receptor
We hypothesize that optimal γδ T cell responses are contingent on pathogen binding to WC1 molecules, especially since we have shown that silencing WC1 results in an inability of γδ T cells from primed animals to respond to the pathogen Leptospira, a model system we have employed extensively
Summary
WC1 family members are T cell co-receptors and pathogen recognition receptors uniquely expressed by the majority of γδ T cells in the blood of ruminants [1] They are Group B scavenger receptor cysteine rich (SRCR) molecules [2] and belong to the CD163 family [2, 3] which includes the murine γδ T cell marker SCART [3, 4]. Following in vivo-sensitization, these WC1+ mycobacterialresponsive bovine γδ T cells have been shown to respond in recall responses in vitro to both protein and non-protein antigens while WC1+ and CD8+ γδ T cells respond to BCG-infected macrophages [9, 11]. Adaptive-like memory γδ T cells are not confined to the bovine model having been described for specific subpopulations of murine γδ T cells [12, 13] and to be sensitized by Listeria monocytogenes [14] and Staphyloccus aureus [15] in vivo while in humans and non-human primates memory γδ T cells responses to mycobacteria [16,17,18], influenza [19], and malaria [20] have been reported
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