Journal
JOURNAL OF LIPID RESEARCH
Volume 48, Issue 1, Pages 127-138Publisher
ELSEVIER
DOI: 10.1194/jlr.M600365-JLR200
Keywords
arachidonic acid; cytolysis; docosahexaenoic acid; membrane microviscosity; surface expression; trafficking
Categories
Funding
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI014584, T32AI007247, R37AI014584] Funding Source: NIH RePORTER
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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 similar to 20-25%. HLA class I surface levels and their rate of endo-plasmic reticulum (ER)-Golgi traffic were also reduced by PUFA treatment. Calibration experiments showed that the similar to 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 similar to 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.
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