T-cell engagement of dendritic cells rapidly rearranges MHC class II transport

• Published in: Nature (London) Vol. 418; no. 6901; pp. 983 - 988
• Main Authors: Ploegh, Hidde L, Boes, Marianne, Cerny, Jan, Massol, Ramiro, Op den Brouw, Marjolein, Kirchhausen, Tom, Chen, Jianzhu
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 29-08-2002; Nature Publishing Group
• Subjects: Animals; Antigen Presentation; Biological and medical sciences; Bone marrow; Cell Differentiation; Cellular biology; Dendritic Cells - cytology; Dendritic Cells - immunology; Dendritic Cells - metabolism; Endosomes - metabolism; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Histocompatibility Antigens Class II - genetics; Histocompatibility Antigens Class II - immunology; Histocompatibility Antigens Class II - metabolism; Immunobiology; Langerhans Cells - cytology; Langerhans Cells - immunology; Langerhans Cells - metabolism; Lymphocyte Activation; Lymphocytes; Mice; Microtubules - metabolism; Monocytes, macrophages; Mutation - genetics; Myeloid cells: ontogeny, maturation, markers, receptors; Peptides; Protein Transport; Proteins; Rodents; T-Lymphocytes - immunology; Dendritic cell; Antigen presentation; Intracellular transport; Rodentia; Class II histocompatibility antigen; Transgenic animal; Cell cell interaction; Ripening; Vertebrata; Mammalia; Mouse; T-Lymphocyte; Endosome
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature01004

Assembly of major histocompatibility complex (MHC) molecules, which present antigen in the form of short peptides to T lymphocytes, occurs in the endoplasmic reticulum; once assembled, these molecules travel from the endoplasmic reticulum to their final destination. MHC class II molecules follow a route that takes them by means of the endocytic pathway, where they acquire peptide, to the cell surface. The transport of MHC class II molecules in 'professional' antigen-presenting cells (APCs) is subject to tight control and responds to inflammatory stimuli such as lipopolysaccharide. To study class II transport in live APCs, we replaced the mouse MHC class II gene with a version that codes for a class II molecule tagged with enhanced green fluorescent protein (EGFP). The resulting mice are immunologically indistinguishable from wild type. In bone-marrow-derived dendritic cells, we observed class II molecules in late endocytic structures with transport patterns similar to those in Langerhans cells observed in situ. We show that tubular endosomes extend intracellularly and polarize towards the interacting T cell, but only when antigen-laden dendritic cells encounter T cells of the appropriate specificity. We propose that such tubulation serves to facilitate the ensuing T-cell response.