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Cell surface HLA-DR-invariant chain complexes are targeted to endosomes by rapid internalization
P A Roche1, C L Teletski, E Stang
1Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852.
Summary
Major histocompatibility complex (MHC) class II molecules are targeted to endosomes via rapid cell surface internalization. The invariant chain mediates this process, crucial for presenting antigens to T cells.
Area of Science:
- Immunology
- Cell Biology
Background:
- Major histocompatibility complex (MHC) class II molecules present peptides from endocytic compartments to CD4+ T cells.
- Functional MHC class II molecules require association with the invariant chain for peptide loading.
- The intracellular transport pathway for MHC class II-peptide complexes is not fully understood.
Purpose of the Study:
- To investigate the intracellular transport route of MHC class II-invariant chain complexes.
- To determine the mechanism by which MHC class II molecules are targeted to endosomes.
Main Methods:
- Utilized a human B-cell line.
- Quantified cell surface MHC class II-invariant chain complexes.
- Measured the surface half-life of these complexes.
- Investigated the role of the invariant chain's cytoplasmic tail in endocytosis.
Main Results:
- A significant population of MHC class II-invariant chain complexes reaches endosomes through rapid cell surface internalization.
- Approximately 3000 complexes internalize per minute.
- Endocytosis is mediated by the cytoplasmic tail of the invariant chain.
- The invariant chain dissociates from MHC class II molecules after internalization.
Conclusions:
- Rapid endocytosis from the cell surface is a major pathway for targeting MHC class II molecules to endosomes.
- This pathway, mediated by the invariant chain, is critical for efficient loading of immunogenic peptides.
- This mechanism contributes to antigen presentation by CD4+ T cells.