title: Immunosuppressive effects of polyunsaturated fatty acids on antigen presentation by human leukocyte antigen class I molecules.
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.
authors.affiliation: Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA. saameshaikh@gmail.com
authors.forename: Saame Raza
authors.initials: SR
authors.lastname: Shaikh
authors.forename: Michael
authors.initials: M
authors.lastname: Edidin
mesh_terms: D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002460:Cell Line; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D017930:Genes, Reporter; D015789:HLA-A2 Antigen / Q000235:genetics / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D010743:Phospholipids / Q000494:pharmacology; D011205:Povidone / Q000494:pharmacology; D014162:Transfection
chemical_list: D005231:Fatty Acids, Unsaturated; D015789:HLA-A2 Antigen; D015395:Histocompatibility Antigens Class I; D010743:Phospholipids; D011205:Povidone