|
|
||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Journal of Lipid Research, Vol. 48, 127-138, January 2007
Copyright © 2007 by American Society for Biochemistry and Molecular Biology
Department of Biology, Johns Hopkins University, Baltimore, MD 21218
Published, JLR Papers in Press, October 30, 2006.
1 To whom correspondence should be addressed. e-mail: 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 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
-6 PUFA arachidonic acid (AA) or
-3 docosahexaenoic acid lowered their susceptibility to lysis by alloreactive CD8+ T cells by
2025%. 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
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
3040%. 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 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.
Supplementary key words arachidonic acid cytolysis docosahexaenoic acid membrane microviscosity surface expression trafficking
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-amino-actinomycin D
![]()
CiteULike
Complore
Connotea
Del.icio.us
Digg
Reddit
Technorati What's this?
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Journal of Biological Chemistry |
| Molecular and Cellular Proteomics | ASBMB Today |