n -3 Polyunsaturated Fatty Acids Impede the TCR Mobility and the TCR-pMHC Interaction of Anti-Viral CD8+ T Cells.

The immune-suppressive effects of omega-3 (n-3) polyunsaturated fatty acids (PUFAs) on T cells have been observed via multiple in vitro and in vivo models. However, the precise mechanism that causes these effects is still undefined. In this study, we investigated whethern-3 PUFAs regulated T cell receptor (TCR) and peptide-major histocompatibility complex (pMHC) interactions. The expansion of anti-viral CD8(+)T cells that endogenously synthesizen-3 PUFAs (FAT-1) dramatically decreased upon lymphocytic choriomeningitis virus (LCMV) infection in vivo. This decrease was not caused by the considerable reduction of TCR expression or the impaired chemotactic activity of T cells. Interestingly, a highly inclined and laminated optical sheet (HILO) microscopic analysis revealed that the TCR motility was notably reduced on the surface of the FAT-1 CD8(+)T cells compared to the wild type (WT) CD8(+)T cells. Importantly, the adhesion strength of the FAT-1 CD8(+)T cells to the peptide-MHC was significantly lower than that of the WT CD8(+)T cells. Consistent with this result, treatment with docosahexaenoic acid (DHA), one type ofn-3 PUFA, significantly decreased CD8(+)T cell adhesion to the pMHC. Collectively, our results reveal a novel mechanism through whichn-3 PUFAs decrease TCR-pMHC interactions by modulating TCR mobility on CD8(+)T cell surfaces.