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Concentration of MHC class II molecules in lipid rafts facilitates antigen presentation

Nature Immunology volume 1, pages 156–162 (2000)Cite this article

Abstract

The plasma membranes of eukaryotic cells are not uniform and possess distinct cholesterol– and sphingolipid–rich raft microdomains that are enriched in proteins known to be essential for cellular function. Lipid raft microdomains are important for T cell receptor (TCR)–mediated activation of T cells. However, the importance of lipid rafts on antigen presenting cells (APCs) and their role in major histocompatibility (MHC) class II–restricted antigen presentation has not been examined. MHC class II molecules were found to be constitutively present in plasma membrane lipid rafts in B cells. Disruption of these microdomains dramatically inhibited antigen presentation at limiting concentrations of antigen. The inhibitory effect of raft disruption on antigen presentation could be overcome by loading the APCs with exceptionally high doses of antigen, showing that raft association concentrates MHC class II molecules into microdomains that allow efficient antigen presentation at low ligand densities.

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Figure 1: Disrupting lipid raft integrity inhibits antigen presentation.
Figure 2: Nystatin inhibits presentation of intact protein and preprocessed peptide antigens to T cells.
Figure 3: Disrupting raft integrity inhibits antigen presentation by MHC class II–expressing fibroblasts.
Figure 4: Raft-disrupting drugs do not alter surface expression or peptide association with MHC class II.
Figure 5: MHC class II molecules are associated with raft microdomains.
Figure 6: Lipid raft marker colocalizes with MHC class II but not CD45R.
Figure 7: MCD disrupts MHC class II association with rafts.
Figure 8: Raft disruption preferentially inhibits antigen presentation at low ligand densities.
Figure 9: Hypothetical model for effects of raft disruption on MHC class II–restricted T cell activation.

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Acknowledgements

We thank D. Winkler for peptide synthesis, J. Ashwell for the cytochrome c-specific 2B4 T cell hybridoma, J. Miller for the class II antiserum, T. Brotz for advice and assistance with our microscopy studies and A. Singer and R. Hodes for discussions and for reading the manuscript.

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Author notes

  1. Howard A. Anderson

    Present address: Laboratory of Immunology, Division of Therapeutic Proteins, FDA/CBER, Bethesda, MD, 20892, USA

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  1. Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, 20892, MD, USA

    Howard A. Anderson, Elizabeth M. Hiltbold & Paul A. Roche

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Correspondence to Paul A. Roche.

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Anderson, H., Hiltbold, E. & Roche, P. Concentration of MHC class II molecules in lipid rafts facilitates antigen presentation. Nat Immunol 1, 156–162 (2000). https://doi.org/10.1038/77842

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