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Atypical MHC class II-expressing antigen-presenting cells: can anything replace a dendritic cell?

Key Points

  • Understanding the function of dendritic cells (DCs) forms the basis of the characterization of professional antigen-presenting cells (APCs). DCs recognize and respond to danger-associated and pathogen-associated signals; express all of the necessary antigen-processing machinery; localize to the T cell zones of secondary lymphoid organs; and express the necessary co-stimulatory molecules and cytokines to activate naive CD4+ T cells.

  • Almost all myeloid-derived cells — including neutrophils, mast cells, basophils and eosinophils — have been shown to upregulate MHC class II molecules in certain settings. There is evidence that these MHC class II-expressing cells may support ongoing T helper (TH2) cell responses but less compelling data that they can prime naive CD4+ T cells.

  • Innate lymphoid cells are a recently described population of cells that can express MHC class II molecules. Recent data conflict as to whether they drive pro-inflammatory or tolerogenic CD4+ T cell responses. As with many other atypical APCs, their function may be dependent on the anatomical site in which their activities are assessed and the specific assays that are used to measure their function.

  • Many epithelial, endothelial and stromal cell populations can express MHC class II. Expression of MHC class II molecules by these cells may contribute to CD4+ T cell tolerance.

  • Many studies that have explored the antigen-presenting functions of atypical APCs have been conducted in mice. A major limitation of the field is that there are few corroborative studies in humans.

Abstract

Dendritic cells, macrophages and B cells are regarded as the classical antigen-presenting cells of the immune system. However, in recent years, there has been a rapid increase in the number of cell types that are suggested to present antigens on MHC class II molecules to CD4+ T cells. In this Review, we describe the key characteristics that define an antigen-presenting cell by examining the functions of dendritic cells. We then examine the functions of the haematopoietic cells and non-haematopoietic cells that can express MHC class II molecules and that have been suggested to represent 'atypical' antigen-presenting cells. We consider whether any of these cell populations can prime naive CD4+ T cells and, if not, question the effects that they do have on the development of immune responses.

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Figure 1: Key antigen-presenting functions of professional and atypical antigen-presenting cells.
Figure 2: Epithelial cells and stromal cells express MHC class II molecules.

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Acknowledgements

Work in the laboratory of T.M.L. is supported by a VA Merit Award. Research in the laboratory of T.K. is supported by funding from the US National Institutes of Health and the American Asthma Foundation.

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Glossary

Experimental autoimmune encephalomyelitis

An experimental model for the human disease multiple sclerosis. Autoimmune disease is induced in experimental animals by immunization with myelin or peptides derived from myelin. The animals develop a paralytic disease with inflammation and demyelination in the brain and spinal cord.

Mixed lymphocyte responses

A tissue-culture technique for testing T cell reactivity. The proliferation of one population of T cells — induced by exposure to inactivated MHC-mismatched stimulator cells — is determined by measuring the incorporation of 3H-thymidine into the DNA of dividing cells.

Macropinocytosis

A type of endocytosis (or phagocytosis) that occurs during the engulfment of apoptotic cells. During macropinocytosis, large droplets of fluid are trapped within the membrane protrusions (ruffles) or phagocytic arms.

Superantigens

Proteins that bind to and activate all T cells that express a particular set of Vβ T cell receptor genes.

Neutrophil extracellular traps

(NETs). A set of extracellular fibres produced by activated neutrophils to ensnare invading microorganisms. NETs enhance neutrophil killing of extracellular pathogens, while minimizing damage to host cells.

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Kambayashi, T., Laufer, T. Atypical MHC class II-expressing antigen-presenting cells: can anything replace a dendritic cell?. Nat Rev Immunol 14, 719–730 (2014). https://doi.org/10.1038/nri3754

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