High fat diets increase TCR nano‐scale clustering

Abstract

High fat diets have immunomodulatory effects on CD4+ T cell frequency, activation, and signaling. However, the mechanisms by which high fat diets modify T cell function remains to be elucidated. One emerging viewpoint is that dietary fatty acids change the plasma membrane's biophysical organization on a nano‐scale, which in turn disrupts T cell receptor (TCR)/co‐receptor distribution and function. In the present study, we tested if high fat diets enriched in either saturated or monounsaturated fatty acids could modify TCR nano‐scale clustering of naïve CD4+ T cells using a new method of quantum dot imaging and k‐space analysis. CD4 transgenic B10.BR mice were fed for 2 weeks a normal diet (5% fat by weight) or high fat diets (20% fat by weight) enriched in saturated (SFA) or monounsaturated (MUFA) fatty acids. Although both high fat diets increased TCR clustering, the SFA‐rich diet had the greatest effect. Splenic CD4+ T cells increased TCR nano‐scale clustering by ~50% suggesting that a SFA‐rich diet can alter the threshold for T cell activation. Our findings are consistent with our recent in vitro studies with SFAs on antigen presenting cells to show that changes in plasma membrane structure can significantly modify lymphocyte function. We suggest that high fat diets can modify the biophysical organization of the TCR, which may explain changes in T cell function of obese individuals.