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Originally published in Science Express on 9 December 2004
Science 28 January 2005:
Vol. 307. no. 5709, pp. 593 - 596
DOI: 10.1126/science.1104904
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Reports

Endogenous MHC Class II Processing of a Viral Nuclear Antigen After Autophagy

Casper Paludan,1,2* Dorothee Schmid,1,2* Markus Landthaler,3 Martina Vockerodt,4 Dieter Kube,5 Thomas Tuschl,3 Christian Münz1,2{dagger}

CD4+ T cells classically recognize antigens that are endocytosed and processed in lysosomes for presentation on major histocompatibility complex (MHC) class II molecules. Here, endogenous Epstein-Barr virus nuclear antigen 1 (EBNA1) was found to gain access to this pathway by autophagy. On inhibition of lysosomal acidification, EBNA1, the dominant CD4+ T cell antigen of latent Epstein-Barr virus infection, slowly accumulated in cytosolic autophagosomes. In addition, inhibition of autophagy decreased recognition by EBNA1-specific CD4+ T cell clones. Thus, lysosomal processing after autophagy may contribute to MHC class II–restricted surveillance of long-lived endogenous antigens including nuclear proteins relevant to disease.

1 Laboratory of Viral Immunobiology, Rockefeller University, New York, NY 10021, USA.
2 Christopher H. Browne Center for Immunology and Immune Diseases, Rockefeller University, New York, NY 10021, USA.
3 Laboratory of RNA Molecular Biology, Rockefeller University, New York, NY 10021, USA.
4 Pediatrics I, Georg August University of Göttingen, 37099 Göttingen, Germany.
5 Center for Internal Medicine, Hematology, and Oncology, Georg August University of Göttingen, 37099 Göttingen, Germany.


* These authors contributed equally to the presented work.

{dagger} To whom correspondence should be addressed. E-mail: munzc{at}mail.rockefeller.edu

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Science. ISSN 0036-8075 (print), 1095-9203 (online)