Submitted on August 16, 2006
Revised on October 30, 2006
Accepted on October 30, 2006
Immunosuppressive effects of polyunsaturated fatty acids on antigen presentation by HLA class I molecules
Saame Raza Shaikh and Michael Edidin
Biology, Johns Hopkins University, Baltimore, MD 21218
Corresponding Author: saameshaikh{at}gmail.com
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 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 -6 PUFA arachidonic acid (AA) or -3 docosahexaenoic acid (DHA) lowered their susceptibility to lysis by alloreactive CD8+ T cells by ~20-25%. HLA class I surface levels and their rate of ER-Golgi traffic were also reduced by PUFA treatment. Calibration experiments showed the ~15% reduction in surface HLA I was not sufficient to completely account for the decreased lysis. However, PUFAs significantly lowered APC-T cell conjugate formation, by ~30-40%. Taken together, our data show for the first time that an -6 and an -3 PUFA affect the HLA class I pathway of B lymphoblasts. Our findings suggest 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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