Transport of Peptide-MHC Class II Complexes in Developing Dendritic Cells

Author:

Turley Shannon J.1,Inaba Kayo2,Garrett Wendy S.1,Ebersold Melanie1,Unternaehrer Julia1,Steinman Ralph M.3,Mellman Ira1

Affiliation:

1. Department of Cell Biology and Section of Immunobiology, Ludwig Institute for Cancer Research, Yale University School of Medicine, 333 Cedar Street, Post Office Box 208002, New Haven, CT 06520–8002, USA.

2. Laboratory of Immunobiology, Graduate School of Biostudies, Kyoto University, Kyoto 606–8502, Japan.

3. Laboratory of Cellular Immunology and Physiology, Rockefeller University, 1230 York Avenue, New York, NY 10021–6399, USA.

Abstract

Major histocompatibility complex class II (MHC II) molecules capture peptides within the endocytic pathway to generate T cell receptor (TCR) ligands. Immature dendritic cells (DCs) sequester intact antigens in lysosomes, processing and converting antigens into peptide–MHC II complexes upon induction of DC maturation. The complexes then accumulate in distinctive, nonlysosomal MHC II + vesicles that appear to migrate to the cell surface. Although the vesicles exclude soluble lysosomal contents and antigen-processing machinery, many contain MHC I and B7 costimulatory molecules. After arrival at the cell surface, the MHC and costimulatory molecules remain clustered. Thus, transport of peptide–MHC II complexes by DCs not only accomplishes transfer from late endocytic compartments to the plasma membrane, but does so in a manner that selectively concentrates TCR ligands and costimulatory molecules for T cell contact.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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