Autophagy and Antigen Presentation

Science's STKE  01 Feb 2005:
Vol. 2005, Issue 269, pp. tw46
DOI: 10.1126/stke.2692005tw46

One-third of all eluted major histocompatibility complex (MHC) class II natural ligands are derived from endogenous cytosolic or nuclear proteins, but the underlying pathway has been difficult to pinpoint. EBNA1, the dominant CD4+ T cell antigen of the human oncogenic Epstein-Barr virus (EBV), is the sole viral antigen present in all EBV-associated malignancies. Paludan et al. describe how autophagy, a process by which the cell degrades defunct cytosolic components in times of stress, leads to MHC class II processing and presentation of endogenous EBNA1. The viral protein was imported into lysosomes by autophagy where a subset of lysosomal proteases was responsible for EBNA1 degradation. Furthermore, inhibition of autophagy decreased target recognition by EBNA1-specific CD4+ T cell clones.

C. Paludan, D. Schmid, M. Landthaler, M. Vockerodt, D. Kube, T. Tuschl, C. Münz, Endogenous MHC class II processing of a viral nuclear antigen after autophagy. Science 307, 593-596 (2005). [Abstract] [Full Text]