Selenoproteins Regulate Antigen Processing and Presentation in Antigen Presenting Cells (P24-024-19)

OBJECTIVES: Selenium (Se), which exerts its effects via selenoproteins, is an essential micronutrient that has been shown to be required for optimal functioning of the immune system. Although numerous studies have examined the effects of selenoproteins on various aspects of the immune response, few studies have investigated the effects of Se on antigen presentation. Moreover, these studies have provided conflicting results indicating the need for further research regarding the effect of Se on Antigen Presenting Cells (APCs). Our goal is to identify the role of selenoproteins in antigen presentation in professional APCs. METHODS: Mice deficient in selenoproteins in a cell specific manner were generated by knocking out the trspgene, which encodes for an essential tRNA for selenocysteine synthesis, utilizing the cre/lox system. The resulting mice are referred to asTrsp(DC)and Trsp(B)representing selenoprotein deficiency specifically in dendritic cells (DCs) and B cells, respectively. Additional studies were done utilizing a diet model of Se deficiency to isolate Se-deficient DCs and B cells. Rate of endocytosis by specific receptors and expression of various surface molecule characteristics of APCs were determined by flow cytometry. Degradation of antigens by APCs in the presence or absence of selenoproteins was measured by western blot. RESULTS: In B cells, selenoprotein deficiency results in a decrease in the number of B220 + Splenocytes, B Cell Receptor (BCR) endocytosis, calcium flux following antigen stimulation, and BCR degradation following internalization. Similarly, selenoprotein deficiency in DCs results in decreased DEC-205 (a collectin-like receptor for multiple antigens) endocytosis; and a reduction in the expression of MHCII, CD80, and CD86. These results suggest a role for selenoproteins during the processing and presentation of peptides to T cells. CONCLUSIONS: Loss of selenoproteins results in the decreased functionality of both B cells and DCs, which suggests that Se and selenoproteins may be involved in the regulation of antigen presentation. Further studies are needed to elucidate the underlying mechanism by which selenoproteins regulate antigen presentation. Such studies are likely to reveal novel targets for enhancing the immune response to vaccines and other specific antigens. FUNDING SOURCES: NIH/NIAID to GK; NIH/GM to SS; NIH/NIDDK to KSP.