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Updated: Aug 19, 2026

Purification of the Membrane Compartment for Endoplasmic Reticulum-associated Degradation of Exogenous Antigens in Cross-presentation
Published on: August 21, 2017
A cytosolic pathway for MHC class II-restricted antigen processing that is proteasome and TAP dependent
Mona K Tewari1, Gomathinayagam Sinnathamby, Deepa Rajagopal
1Department of Microbiology & Immunology, Kimmel Cancer Institute, Thomas Jefferson University, 233 S. 10th Street, BLSB 730, Philadelphia, Pennsylvania 19107, USA.
Abstract:
By convention, presentation of major histocompatibility complex (MHC) class I-restricted epitopes involves processing by cytosolic proteasomes, whereas MHC class II-restricted epitopes are generated by endosomal proteases. Here, we show that two MHC class II-restricted epitopes within influenza virus were generated by a proteasome- and TAP-dependent pathway that was accessed by exogenous virus in dendritic cells (DCs) but not cell types with less permeable endosomes. Both epitopes were presented by recycling MHC class II molecules. Challenging mice with influenza or vaccinia viruses demonstrated that a substantial portion of the MHC class II-restricted response was directed against proteasome-dependent epitopes. By complementing endosomal activities, this pathway broadens the array of MHC class II-restricted epitopes available for CD4(+) T cell activation.
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