Variegated Transcription of the WC1 Hybrid PRR/Co-Receptor Genes by Individual γδ T Cells and Correlation With Pathogen Responsiveness

gamma delta T cells have broad reactivity and actively participate in protective immunity against tumors and infectious disease-causing organisms. In gamma delta-high species such as ruminants and other artiodactyls many gamma delta 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 gamma delta 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 gamma delta T cell receptor. WC1(+) gamma delta 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 gamma delta T cell responses are contingent on pathogen binding to WC1 molecules, especially since we have shown that silencing WC1 results in an inability of gamma delta 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 gamma delta T cell biology, the pattern of WC1 gene expression by individual gamma delta T cells was not known but is critical to devise methods to engage gamma delta T cells for responses to specific pathogens. To address this gap, we generated 78 gamma delta 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 gamma delta T cell clones were shown to have a significantly higher propensity to express WC1 molecules that are known to bind to the pathogen.