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Lipid Overload with Saturated and Monounsaturated Fatty Acids Has Differential Effects on MHC Class I Antigen Presentation
Author(s) -
Shaikh Saame Raza,
Li Matt,
Schneck Jonathan,
Edidin Michael
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.150.3
Subject(s) - antigen presentation , antigen , major histocompatibility complex , mhc class ii , adipose tissue , mhc class i , immune system , antigen presenting cell , chemistry , cytotoxic t cell , immunology , biology , medicine , biochemistry , t cell , in vitro
Lipid overload, associated with obesity, occurs when saturated fatty acids (SFAs) accumulate in non‐adipose tissues. Cells of these tissues use major histocompatibility (MHC) class I molecules to present antigen to cytolytic T lymphocytes (CTLs) in order to eliminate pathogens. Since obesity is associated with impaired immune responses, we tested if lipid overload with SFAs could affect MHC class I antigen presentation to CTLs. Antigen presenting cells (APCs) were fed either the saturated fatty acid palmitic acid (PA) or the monounsaturated oleic acid (OA), which are respectively major components of the high fat Western or Mediterranean diets. PA‐feeding lowered APC lysis by activated CTLs and inhibited the ability of APCs to stimulate naïve T cells. Inhibition of immune responses with PA was due to lowered MHC class I surface expression and inhibition in the rate of APC‐CTL conjugation. These changes were associated with a modification of plasma membrane acyl chain structure and F‐actin levels, which could modify the immunological synapse. OA‐treatment had no effect on antigen presentation and when fed together with PA, blocked the effects of PA. This block with OA correlated with its distinct cellular metabolic fate. OA‐treatment conferred protection by accumulating fatty acids into triglyceride‐rich lipid droplets of APCs. Our findings establish a link between lipid overload and antigen presentation and suggest that dietary SFAs in non‐adipose cells of obese individuals could impair immunity by affecting MHC I‐mediated antigen presentation; this could be prevented by accumulation of triglycerides rich in monounsaturated fatty acids.