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Nat Immunol. 2005 Mar;6(3):287-94. Epub 2005 Feb 13.

A cytosolic pathway for MHC class II-restricted antigen processing that is proteasome and TAP dependent.

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Department of Microbiology & Immunology, Kimmel Cancer Institute, Thomas Jefferson University, 233 S. 10th Street, BLSB 730, Philadelphia, Pennsylvania 19107, USA.

Erratum in

  • Nat Immunol. 2005 Apr;6(4):420.


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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