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

Nature Immunologyvolume 6pages287294 (2005) | Download Citation

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  • A Corrigendum to this article was published on 01 April 2005

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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Acknowledgements

We thank S. Luke at the Kimmel Cancer Institute bioimaging facility and J. Faust and A. Acosta at the Wistar flow cytometry facility for outstanding technical assistance. This research was supported by grants from the US National Institutes of Health (AI036331) and the Leukemia and Lymphoma Society (1121-00). M.K.T. is a recipient of a National Research Service Award (T32-CA09683).

Author information

Author notes

    • Deepa Rajagopal

    Present address: National Institute of Immunology, Aruna Asaf Ali Road, New Delhi, 110067, India

Affiliations

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

    • Mona K Tewari
    • , Gomathinayagam Sinnathamby
    • , Deepa Rajagopal
    •  & Laurence C Eisenlohr

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Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Laurence C Eisenlohr.

Supplementary information

  1. Supplementary Fig. 1

    Specificity of NA79 T cell hybridomas. (PDF 87 kb)

  2. Supplementary Fig. 2

    Effect of epoxomicin on S3 presentation from increasing doses of infections PR8. (PDF 123 kb)

  3. Supplementary Fig. 3

    Presentation of S3 from exogenous virus is completely inhibited by lactacystin. (PDF 83 kb)

  4. Supplementary Fig. 4

    Role of H-2M in presentation of S1 and proteasome dependent S3 and NA70 epitopes. (PDF 85 kb)

  5. Supplementary Fig. 5

    Proteasome-dependent epitopes can generate immune responses in vivo as measured by synthetic peptides. (PDF 96 kb)

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DOI

https://doi.org/10.1038/ni1171

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