Abstract
MODELS for antigen presentation have divided the world of antigens into two categories, endogenous and exogenous1–3, presented to T cells by class I and class II major histocompatibility complex (MHC) encoded molecules, respectively. Exogenous antigens are thought to be taken up into peripheral endosomal compartments where they are processed for binding to class II MHC molecules. Endogenous antigens are either synthesized4–6or efficiently delivered to the cytoplasm7,8before being partially degraded in an as yet undefined way, and complexed with class I MHC molecules. A useful phenotypic distinction between the two pathways has been the sensitivity to weak bases, such as chloroquine, which is a property only of the exogenous pathway1. The fungal antibiotic brefeldin A (BFA), which blocks protein transport from the endoplasmic reticulum to the Golgi network9–11, also blocks class I-restricted antigen-presentation, providing us with the corresponding marker of the endogenous pathway12,13. Experiments with influenza virus antigens1,14 have supported the view that class II MHC molecules can present exogenous but not endogenous antigen1–3, whereas the observation that class II MHC molecules present measles virus non-membrane antigens by a chloroquine-insensitive pathway15suggests that this is not always the case. We show here that influenza A matrix protein can be effectively presented to class II-restricted T cells by two pathways: one of which is chloroquine-sensitive, BFA-insensitive, the other being chloro-quine-insensitive and BFA-sensitive. Our results indicate that both class I and class II molecules can complex with antigenic peptides in a pre-Golgi compartment and favour a unified mechanism for MHC-restricted endogenous antigen presentation.
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Nuchtern, J., Biddison, W. & Klausner, R. Class II MHC molecules can use the endogenous pathway of antigen presentation. Nature 343, 74–76 (1990). https://doi.org/10.1038/343074a0
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DOI: https://doi.org/10.1038/343074a0
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