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

Abstract

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 surface1. 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.

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Figure 1: Generation and characterization of MHC II-EGFP knock-in mice.
Figure 2: MHC II-EGFP molecules in dendritic cells reside in late endosomes.
Figure 3: Transport of MHC II-EGFP-containing structures in Langerhans cells in situ.
Figure 4: Microtubule-driven directional transport of endosomal compartments on T-cell contact.
Figure 5: Primary T cells induce tubulation in dendritic cells in an antigen-dependent manner.

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Acknowledgements

We thank M. Boxem for help in designing the targeting construct and T. Schmidt for blastocyst microinjections. We thank A. W. M. van der Velden for providing DsRed1-labelled S. typhimurium, and we acknowledge discussions with members of the Ploegh laboratory.

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Correspondence to Hidde L. Ploegh.

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Boes, M., Cerny, J., Massol, R. et al. T-cell engagement of dendritic cells rapidly rearranges MHC class II transport. Nature 418, 983–988 (2002). https://doi.org/10.1038/nature01004

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