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Direct Antigen Presentation and Gap Junction Mediated Cross-Presentation during Apoptosis¹

Baoxu Pang^*,2, Joost Neijssen^*,2, Xiaohang Qiao^*,, Lennert Janssen^*, Hans Janssen^*, Christoph Lippuner^*,3 and Jacques Neefjes^*,4

*Division of Cell Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands; and Center for Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China, and the Graduate School of the Chinese Academy of Sciences, Beijing, China

MHC class I molecules present peptides from endogenous proteins. Ags can also be presented when derived from extracellular sources in the form of apoptotic bodies. Cross-presentation of such Ags by dendritic cells is required for proper CTL responses. The fate of Ags in cells initiated for apoptosis is unclear as is the mechanism of apoptosis-derived Ag transfer into dendritic cells. Here we show that novel Ags can be generated by caspases and be presented by MHC class I molecules of apoptotic cells. Since gap junctions function until apoptotic cells remodel to form apoptotic bodies, transfer and cross-presentation of apoptotic peptides by neighboring and dendritic cells occurs. We thus define a novel phase in classical Ag presentation and cross-presentation by MHC class I molecules: presentation of Ags created by caspase activities in cells in apoptosis.

⁴ Address correspondence and reprint requests to Dr. Jacques Neefjes, Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX Amsterdam, The Netherlands. E-mail address: j.neefjes{at}nki.nl

¹ This work was supported by a grant from the Dutch Cancer Society (KWF).

² B.P. and J.N. contributed equally to this work.

³ Current address: Vetsuisse Faculty, University Zürich, and Institute of Parasitology and Section of Herd Health Management (Department of Farm Animals), Winterthurerstrasse 266a, CH-8057 Zürich, Switzerland.