Immunosuppressive effects of polyunsaturated fatty acids on antigen presentation by human leukocyte antigen class I molecules

Saame Raza Shaikh¹ and Michael Edidin

Department of Biology, Johns Hopkins University, Baltimore, MD 21218

Published, JLR Papers in Press, October 30, 2006.

^¹ To whom correspondence should be addressed. e-mail: saameshaikh{at}gmail.com

Dietary supplementation with polyunsaturated fatty acids (PUFAs)has immunosuppressive effects; however, the molecular targetsof PUFAs and their mode of action remain unclear. One possibletarget is antigen presentation to T cells through the humanleukocyte antigen (HLA) class I pathway. Here we show that incorporationof PUFAs lowers target cell susceptibility to lysis by effectorT cells. Treatment of B lymphoblast targets with the ${omega}$ -6 PUFAarachidonic acid (AA) or ${omega}$ -3 docosahexaenoic acid lowered theirsusceptibility to lysis by alloreactive CD8⁺ T cells by $~$ 20–25%.HLA class I surface levels and their rate of endoplasmic reticulum(ER)-Golgi traffic were also reduced by PUFA treatment. Calibrationexperiments showed that the $~$ 15% reduction in surface HLA I wasnot sufficient to completely account for the decreased lysis.However, PUFAs significantly lowered antigen-presenting cell-Tcell conjugate formation, by $~$ 30–40%. Taken together, ourdata show for the first time that an ${omega}$ -6 and an ${omega}$ -3 PUFA affectthe HLA class I pathway of B lymphoblasts. Our findings suggestthat elimination of self- and pathogen-derived peptides by effectorsmay be compromised by dietary PUFA supplementation. In addition,PUFA-mediated changes in ER-Golgi trafficking point to a newarea of PUFA modulation of immune responses.

Supplementary key words arachidonic acid • cytolysis • docosahexaenoic acid • membrane microviscosity • surface expression • trafficking

Abbreviations: AA, arachidonic acid; APC, antigen-presenting cell; BFA, Brefeldin A; BHT, butylated hydroxytoluene; CTL, cytotoxic T lymphocyte; DHA, docosahexaenoic acid; ER, endoplasmic reticulum; FACS, fluorescence-activated cell sorting; HBSS, Hanks' balanced salt solution; HLA, human leukocyte antigen; NL, neutral lipid; PA, palmitic acid; PC, phosphatidylcholine; PUFA, polyunsaturated fatty acid; PVP, polyvinylpyrollidone; TCR, T cell receptor; 7-AAD, 7-amino-actinomycin D

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