Cells of the immune system recognize disease-causing pathogens and respond in a manner to stop the infection. While we know how conventional cells of the immune system do this, for some non-conventional cells such as gamma delta T cells this process is less clear. Bovine gamma delta T cells bear lineage-specific transmembrane glycoproteins known as WC1. We have shown that they are coded for by a multigenic family and these molecules function both as pattern recognition receptors (PRR) and signaling co-receptors for cellular activation. For example, a subpopulation of gamma delta T cells known as WC1.1+ cells respond early and before CD4 T cells following vaccination against Leptospira borgpetersenii serovar harjo, proliferating and producing interferon-gamma. They continue to respond in in vitro recall responses for months following vaccination while other subpopulations of gamma delta T cells that express a different set of the WC1 genes do not respond. We have shown that WC1 molecules on gamma delta T cells that respond to Leptospira bind the bacteria and that the WC1 molecules are essential for maximal gamma delta T cell responses. Thus, we hypothesize that the WC1 family members expressed by a particular cell will determine its ability to respond to an infection. To test this hypothesis we have evaluated the distribution of WC1 gene expression among individual gamma delta T cell clones that respond to leptospira and find they express WC1 molecules known to bind leptospira. We propose that vaccines could be designed to activate gamma delta T cells through engagement of the WC1 co-receptor with the T cell receptor to stimulate rapid responses by interferon-gamma-producing gamma delta T cells that could influence the development of a Th1 CD4 T cell response.