γδ T cells recognize a microbial encoded B cell antigen to initiate a rapid antigen-specific interleukin-17 response.

γδ T cells contribute uniquely to immune competence. Nevertheless, how they function remains an enigma. It is unclear what most γδ T cells recognize, what is required for them to mount an immune response, and how the γδ T cell response is integrated into host immune defense. Here, we report that a noted B cell antigen, the algae protein phycoerythrin (PE), is a murine and human γδ T cell antigen. Employing this specificity, we demonstrated that antigen recognition activated naive γδ T cells to make interleukin-17 and respond to cytokine signals that perpetuate the response. High frequencies of antigen-specific γδ T cells in naive animals and their ability to mount effector response without extensive clonal expansion allow γδ T cells to initiate a swift, substantial response. These results underscore the adaptability of lymphocyte antigen receptors and suggest an antigen-driven rapid response in protective immunity prior to the maturation of classical adaptive immunity.

Evolution of the CD163 family and its relationship to the bovine gamma delta T cell co-receptor WC1.

BACKGROUND: The scavenger receptor cysteine rich (SRCR) domain is an ancient and conserved protein domain. CD163 and WC1 molecules are classed together as group B SRCR superfamily members, along with Spalpha, CD5 and CD6, all of which are expressed by immune system cells. There are three known types of CD163 molecules in mammals, CD163A (M130, coded for by CD163), CD163b (M160, coded for by CD163L1) and CD163c-alpha (CD163L1 or SCART), while their nearest relative, WC1, is encoded by a multigene family so far identified in the artiodactyl species of cattle, sheep, and pigs. RESULTS: We annotated the bovine genome and identified genes coding for bovine CD163A and CD163c-alpha but found no evidence for CD163b. Bovine CD163A is widely expressed in immune cells, whereas CD163c-alpha transcripts are enriched in the WC1+ gammadelta T cell population. Phylogenetic analyses of the CD163 family genes and WC1 showed that CD163c-alpha is most closely related to WC1 and that chicken and platypus have WC1 orthologous genes, previously classified as among their CD163 genes. CONCLUSION: Since it has been shown that WC1 plays an important role in the regulation of gammadelta T cell responses in cattle, which, like chickens, have a high percentage of gammadelta T cells in their peripheral blood, CD163c-alpha may play a similar role, especially in species lacking WC1 genes. Our results suggest that gene duplications resulted in the expansion of CD163c-alpha-like and WC1-like molecules. This expanded repertoire was retained by species known as "gammadelta T cell high", but homologous SRCR molecules were maintained by all mammals.