CD8+T Cell Cross-Priming via Transfer of Proteasome Substrates

• Published in: Science (American Association for the Advancement of Science) 2004-05, Vol.304 (5675), p.1318-1321
• Main Authors: Norbury, Christopher C., Basta, Sameh, Donohue, Keri B., Tscharke, David C., Princiotta, Michael F., Berglund, Peter, Gibbs, James, Bennink, Jack R., Yewdell, Jonathan W.
• Format: Article
• Language: English
• Subjects: Acetylcysteine - analogs & derivatives; Acetylcysteine - pharmacology; Animals; Antigen Presentation; Antigen presenting cells; Antigens; Antigens - immunology; Antigens - metabolism; Antigens, Viral - immunology; Antigens, Viral - metabolism; Biological and medical sciences; CD8-Positive T-Lymphocytes - immunology; Cell Line; Cell lines; Cross priming; Cysteine Endopeptidases - metabolism; Cysteine Proteinase Inhibitors - pharmacology; Endoplasmic Reticulum - metabolism; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Immunization; Immunobiology; Infections; Influenza A virus - immunology; Lymphocyte Activation; Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation; Mice; Mice, Inbred C57BL; Mice, Transgenic; Molecular chaperones; Molecular Chaperones - metabolism; Molecules; Multienzyme Complexes - metabolism; Ovalbumin - immunology; Ovalbumin - metabolism; Peptide Fragments - immunology; Proteasome Endopeptidase Complex; Recombinant Fusion Proteins - immunology; Recombinant Fusion Proteins - metabolism; Splenocytes; T lymphocytes; Vaccines - immunology; Vaccinia virus - genetics; Vaccinia virus - physiology; Viruses
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1096378

"Cross-priming" describes the activation of$na\ddot{i}ve$CD8+T cells by professional antigen-presenting cells that have acquired viral or tumor antigens from "donor" cells. Antigen transfer is believed to be mediated by donor cell-derived molecular chaperones bearing short peptide ligands generated by proteasome degradation of protein antigens. We show here that crosspriming is based on the transfer of proteasome substrates rather than peptides. These findings are potentially important for the rational design of vaccines that elicit CD8+T cell responses.