Abstract
Dietary supplementation with polyunsaturated fatty acids (PUFAs) has immunosuppressive effects; however, the molecular targets of PUFAs and their mode of action remain unclear. One possible target is antigen presentation to T cells through the human leukocyte antigen (HLA) class I pathway. Here we show that incorporation of PUFAs lowers target cell susceptibility to lysis by effector T cells. Treatment of B lymphoblast targets with the omega-6 PUFA arachidonic acid (AA) or omega-3 docosahexaenoic acid lowered their susceptibility to lysis by alloreactive CD8+ T cells by approximately 20-25%. HLA class I surface levels and their rate of endoplasmic reticulum (ER)-Golgi traffic were also reduced by PUFA treatment. Calibration experiments showed that the approximately 15% reduction in surface HLA I was not sufficient to completely account for the decreased lysis. However, PUFAs significantly lowered antigen-presenting cell-T cell conjugate formation, by approximately 30-40%. Taken together, our data show for the first time that an omega-6 and an omega-3 PUFA affect the HLA class I pathway of B lymphoblasts. Our findings suggest that elimination of self- and pathogen-derived peptides by effectors may be compromised by dietary PUFA supplementation. In addition, PUFA-mediated changes in ER-Golgi trafficking point to a new area of PUFA modulation of immune responses.
Highlights
Dietary supplementation with polyunsaturated fatty acids (PUFAs) has immunosuppressive effects; the molecular targets of PUFAs and their mode of action remain unclear
An important finding from this study was that the expression of one HLA class I epitope, measured by 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-amino-actinomycin D (7-AAD), 7-aminoactinomycin D
We show that PUFA modification alters the surface expression of HLA class I molecules as a result of a reduced rate of forward trafficking of newly synthesized molecules from the endoplasmic reticulum (ER) to the Golgi, but the reduction in surface HLA class I molecules is not sufficient to completely account for reduced lysis
Summary
Dietary supplementation with polyunsaturated fatty acids (PUFAs) has immunosuppressive effects; the molecular targets of PUFAs and their mode of action remain unclear. A few studies have shown that v-3 PUFAs can lower the surface expression of human leukocyte antigen (HLA) class II molecules, with concomitant reductions in antigen presentation [13, 14]. An important finding from this study was that the expression of one HLA class I epitope, measured by 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-aminoactinomycin D. A major limitation of the in vitro functional experiments by Jenski was the lack of saturated lipid controls and a nonphysiological method of lipid delivery
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