Immunosuppressive effects of polyunsaturated fatty acids on antigen presentation by human leukocyte antigen class I molecules

Saame Raza Shaikh, Michael A Edidin

Research output: Contribution to journalArticle

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 ω-6 PUFA arachidonic acid (AA) or ω-3 docosahexaenoic acid lowered their susceptibility to lysis by alloreactive CD8+ T cells by ∼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 ∼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 ∼30-40%. Taken together, our data show for the first time that an ω-6 and an ω-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.

Original languageEnglish (US)
Pages (from-to)127-138
Number of pages12
JournalJournal of Lipid Research
Volume48
Issue number1
DOIs
StatePublished - Jan 2007

Fingerprint

Antigen Presentation
Antigens
Immunosuppressive Agents
HLA Antigens
Unsaturated Fatty Acids
Molecules
T-cells
T-Lymphocytes
Endoplasmic Reticulum
Docosahexaenoic Acids
Pathogens
Antigen-Presenting Cells
Dietary Supplements
Arachidonic Acid
Calibration
Modulation
Peptides

Keywords

  • Arachidonic acid
  • Cytolysis
  • Docosahexaenoic acid
  • Membrane microviscosity
  • Surface expression
  • Trafficking

ASJC Scopus subject areas

  • Endocrinology

Cite this

Immunosuppressive effects of polyunsaturated fatty acids on antigen presentation by human leukocyte antigen class I molecules. / Shaikh, Saame Raza; Edidin, Michael A.

In: Journal of Lipid Research, Vol. 48, No. 1, 01.2007, p. 127-138.

Research output: Contribution to journalArticle

@article{d3ec974120064d1f92c1468a16eef551,
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 ω-6 PUFA arachidonic acid (AA) or ω-3 docosahexaenoic acid lowered their susceptibility to lysis by alloreactive CD8+ T cells by ∼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 ∼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 ∼30-40{\%}. Taken together, our data show for the first time that an ω-6 and an ω-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.",
keywords = "Arachidonic acid, Cytolysis, Docosahexaenoic acid, Membrane microviscosity, Surface expression, Trafficking",
author = "Shaikh, {Saame Raza} and Edidin, {Michael A}",
year = "2007",
month = "1",
doi = "10.1194/jlr.M600365-JLR200",
language = "English (US)",
volume = "48",
pages = "127--138",
journal = "Journal of Lipid Research",
issn = "0022-2275",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "1",

}

TY - JOUR

T1 - Immunosuppressive effects of polyunsaturated fatty acids on antigen presentation by human leukocyte antigen class I molecules

AU - Shaikh, Saame Raza

AU - Edidin, Michael A

PY - 2007/1

Y1 - 2007/1

N2 - 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 ω-6 PUFA arachidonic acid (AA) or ω-3 docosahexaenoic acid lowered their susceptibility to lysis by alloreactive CD8+ T cells by ∼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 ∼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 ∼30-40%. Taken together, our data show for the first time that an ω-6 and an ω-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.

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 ω-6 PUFA arachidonic acid (AA) or ω-3 docosahexaenoic acid lowered their susceptibility to lysis by alloreactive CD8+ T cells by ∼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 ∼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 ∼30-40%. Taken together, our data show for the first time that an ω-6 and an ω-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.

KW - Arachidonic acid

KW - Cytolysis

KW - Docosahexaenoic acid

KW - Membrane microviscosity

KW - Surface expression

KW - Trafficking

UR - http://www.scopus.com/inward/record.url?scp=33845991474&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33845991474&partnerID=8YFLogxK

U2 - 10.1194/jlr.M600365-JLR200

DO - 10.1194/jlr.M600365-JLR200

M3 - Article

VL - 48

SP - 127

EP - 138

JO - Journal of Lipid Research

JF - Journal of Lipid Research

SN - 0022-2275

IS - 1

ER -