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Inflammatory stimuli induce accumulation of MHC class II complexes on dendritic cells

Nature volume 388, pages 782–787 (1997)Cite this article

Abstract

Dendritic cells have the remarkable property of presenting any incoming antigen1. To do so they must not only capture antigens with high efficiency and broad specificity, but must also maximize their capacity to load class II molecules of the major histocompatibility complex (MHC) with antigenic peptides in order to present a large array of epitopes from different proteins, each at a sufficient copy number. Here we show that formation of peptide–MHC class II complexes is boosted by inflammatory stimuli that induce maturation of dendritic cells. In immature dendritic cells, class II molecules are rapidly internalized and recycled, turning over with a half-life of about 10 hours. Inflammatory stimuli induce a rapid and transient boost of class II synthesis, while the half-life of class II molecules increases to over 100 hours. These coordinated changes result in the rapid accumulation of a large number of long-lived peptide-loaded MHC class II molecules capable of stimulating T cells even after several days. The capacity of dendritic cells to load many antigenic peptides over a short period of initial exposure to inflammatory stimuli could favour presentation of infectious antigens.

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Figure 1: Increased expression of surface and total class II molecules in DC stimulated with LPS or TNF-α.
Figure 2: Extensive internalization and recycling of MHC class II molecules in immature DC is progressively lost together with endocytic activity following maturation.
Figure 3: Immature DC can efficiently load antigenic peptides on both recycling and newly synthesized MHC class II molecules.
Figure 4: Transient upregulation of MHC class II synthesis in maturing DC.
Figure 5: Maturation increases generation of SDS-stable class II dimers containing antigenic peptides.
Figure 6: Maturation stimuli increase the half-life of class II molecules from ∼10 to >100 hours.
Figure 7: Maturation allows DC to maintain memory of antigens encountered.

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Acknowledgements

We thank D. Scheidegger and M. Dessing for technical assistance, E. Long for discussion, and C. Watts, F. Sallusto, K. Karjalainen and M. Colonna for critically reading the manuscript. The Basel Institute for Immunology was founded and is supported by F. Hoffmann-La Roche, Basel, Switzerland.

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  1. Basel Institute for Immunology, Grenzacherstrasse 487, CH 4005, Basel, Switzerland

    Marina Cella, Anneke Engering, Jean Pieters & Antonio Lanzavecchia

  2. Laboratoire d'Immunologie, Inserm U-291, Hôpital Saint Eloi, 34295, Montpellier, France

    Valerie Pinet

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  1. Marina Cella
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Correspondence to Marina Cella.

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Cella, M., Engering, A., Pinet, V. et al. Inflammatory stimuli induce accumulation of MHC class II complexes on dendritic cells. Nature 388, 782–787 (1997). https://doi.org/10.1038/42030

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