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MHC class I antigen presentation is downregulated by polyunsaturated fatty acids
Author(s) -
Shaikh Saame Raza,
Edidin Michael
Publication year - 2007
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.21.5.a63-c
Subject(s) - polyunsaturated fatty acid , docosahexaenoic acid , mhc class i , antigen presentation , t cell , cd8 , immune system , arachidonic acid , mhc class ii , glycan , chemistry , biology , microbiology and biotechnology , immunology , biochemistry , fatty acid , enzyme , glycoprotein
Polyunsaturated fatty acids, PUFAs, can be used as adjuvant immunosuppressants for alleviating symptoms associated with inflammatory disorders. However, it is unclear if PUFA's immunosuppressive effects also alter susceptibility to infection. Here we show that PUFAs downregulate T cell immune responses in vitro by modulating MHC class I antigen presentation. Incorporation of the ω‐6 PUFA arachidonic acid (AA) or the ω‐3 PUFA docosahexaenoic acid (DHA) into membrane lipids of antigen‐presenting cells, APCs, alters membrane microviscosity, increases lipid droplet formation and significantly reduces susceptibility of the cells to lysis by CD8 + T cells. PUFA modification lowers MHC class I surface expression by lowering the rate of forward trafficking of newly synthesized molecules from the ER to Golgi; however, calibration experiments show this reduction in surface MHC I expression is not sufficient to account for reduced lysis. PUFA treatment also lowers APC‐T cell conjugate formation suggesting that AA and DHA could lower lysis by interfering with the formation of the immunological synapse as a consequence of changes in the lipid profile of APCs. Our data suggest that elimination of pathogen‐derived peptides could be compromised by using PUFAs as immunosuppressants. In addition, PUFA mediated changes in trafficking of MHC class I molecules point to a new area of lipid modulation of immune responses. Funding from the NIH to M.E.