PMID- 17074926 OWN - NLM STAT- MEDLINE DCOM- 20070716 LR - 20210217 IS - 0022-2275 (Print) IS - 0022-2275 (Linking) VI - 48 IP - 1 DP - 2007 Jan TI - Immunosuppressive effects of polyunsaturated fatty acids on antigen presentation by human leukocyte antigen class I molecules. PG - 127-38 AB - 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. FAU - Shaikh, Saame Raza AU - Shaikh SR AD - Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA. saameshaikh@gmail.com FAU - Edidin, Michael AU - Edidin M LA - eng GR - 5T32 AI-07247/AI/NIAID NIH HHS/United States GR - AI-14584/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20061030 PL - United States TA - J Lipid Res JT - Journal of lipid research JID - 0376606 RN - 0 (Fatty Acids, Unsaturated) RN - 0 (HLA-A2 Antigen) RN - 0 (Histocompatibility Antigens Class I) RN - 0 (Phospholipids) RN - FZ989GH94E (Povidone) SB - IM MH - Antigen-Presenting Cells/drug effects/*immunology MH - B-Lymphocytes/drug effects/*immunology MH - Cell Line MH - Fatty Acids, Unsaturated/*pharmacology MH - Genes, Reporter MH - HLA-A2 Antigen/genetics/immunology MH - Histocompatibility Antigens Class I/*immunology MH - Humans MH - Phospholipids/pharmacology MH - Povidone/pharmacology MH - Transfection EDAT- 2006/11/01 09:00 MHDA- 2007/07/17 09:00 CRDT- 2006/11/01 09:00 PHST- 2006/11/01 09:00 [pubmed] PHST- 2007/07/17 09:00 [medline] PHST- 2006/11/01 09:00 [entrez] AID - S0022-2275(20)43643-0 [pii] AID - 10.1194/jlr.M600365-JLR200 [doi] PST - ppublish SO - J Lipid Res. 2007 Jan;48(1):127-38. doi: 10.1194/jlr.M600365-JLR200. Epub 2006 Oct 30.