Advanced Immunology I (Feb. 6, 2004) Yueh-hsiu Chien The source of Antigenic Peptides Associated with Class I MHC Molecules (What is known then, what is new now) N. Shastri, S. Schwab and T. Serwold, Producing nature's gene-chips: the generation of peptides for display by MHC class I molecules. Annu. Rev. Immunol. 20 (2002), pp. 463–493. New vs. Old 1. U. Schubert, L.C. Anton, J. Gibbs, C.C. Norbury, J.W. Yewdell and J.R. Bennink, Rapid degradation of a large fraction of newly synthesized proteins by proteasomes. Nature 404 (2000), pp. 770–774. 2. E.A. Reits, J.C. Vos, M. Gromme and J. Neefjes, The major substrates for TAP in vivo are derived from newly synthesized proteins. Nature 404 (2000), pp. 774–778. 3. E.A. Reits, A. Griekspoor, J. Neijssen, T. Groothuis, K. Jalink, P. van Veelen, H. Janssen, J. Calafat, J.W. Drijfhout and J. Neefjes, Peptide diffusion, protection and degradation in nuclear and cytoplasmic compartments before antigen presentation by MHC class I. Immunity 18 (2003), pp. 97–108. 4. S. Khan, R. de Giuli, G. Schmidtke, M. Bruns, M. Buchmeier, M. van den Broek and M. Groettrup, Cutting edge: neosynthesis is required for the presentation of a T cell epitope from a long-lived viral protein. J. Immunol. 167 (2001), pp. 4801–4804. 5. J. Levitskaya, M. Coram, V. Levitsky, S. Imreh, P.M. Steigerwald-Mullen, G. Klein, M.G. Kurilla and M.G. Masucci, Inhibition of antigen processing by the internal repeat region of the Epstein-Barr virus nuclear antigen-1. Nature 375 (1995), pp. 685–688. 6. Y. Yin, B. Manoury and R. Fahraeus, Self-inhibition of synthesis and antigen presentation by Epstein-Barr virus-encoded EBNA1. Science 301 (2003), pp. 1371–1374. 7. M.F. Princiotta, D. Finzi, S.B. Qian, J. Gibbs, S. Schuchmann, F. Buttgereit, J.R. Bennink and J.W. Yewdell, Quantitating protein synthesis, degradation, and endogenous antigen processing. Immunity 18 (2003), pp. 343–354. (A comprehensive study on the dynamics of protein turnover and the efficiency of generating MHC class I assembled peptides) 1 Coding vs. Noncoding 8 S.R. Schwab, K.C. Li, C. Kang and N. Shastri, Constitutive display of cryptic translation products by MHC class I molecules. Science 301 (2003), pp. 1367–1371. Inside vs. Outside 9. J. Garin, R. Diez, S. Kieffer, J.F. Dermine, S. Duclos, E. Gagnon, R. Sadoul, C. Rondeau and M. Desjardins, The phagosome proteome: insight into phagosome functions. J. Cell Biol. 152 (2001), pp. 165–180. 10. E. Gagnon, S. Duclos, C. Rondeau, E. Chevet, P.H. Cameron, O. Steele-Mortimer, J. Paiement, J.J. Bergeron and M. Desjardins, Endoplasmic reticulum-mediated phagocytosis is a mechanism of entry into macrophages. Cell 110 (2002), pp. 119–131. 11. B. Tsai, Y. Ye and T.A. Rapoport, Retro-translocation of proteins from the endoplasmic reticulum into the cytosol. Nat. Rev. Mol. Cell. Biol. 3 (2002), pp. 246–255. 12.M. Houde, S. Bertholet, E. Gagnon, S. Brunet, G. Goyette, A. Laplante, M.F. Princiotta, P. Thibault, D. Sacks and M. Desjardins, Phagosomes are competent organelles for antigen cross-presentation. Nature 425 (2003), pp. 402–406. 13. P. Guermonprez, L. Saveanu, M. Kleijmeer, J. Davoust, P. Van Endert and S. Amigorena, ER-phagosome fusion defines an MHC class I crosspresentation compartment in dendritic cells. Nature 425 (2003), pp. 397– 402. 14. A.L. Ackerman, C. Kyritsis, R. Tampe and P. Cresswell, Early phagosomes in dendritic cells form a cellular compartment sufficient for cross presentation of exogenous antigens. Proc. Natl. Acad. Sci. USA 100 (2003), pp. 12889–12894. 2