Research Interest
My name is Jacques Neefjes and I am heading a group at the Division of Cell Biology at the Netherlands Cancer Institute in Amsterdam. I am trained as a chemist but became interested in Cell Biology and Immunology. I graduated with Prof Dr Hidde Ploegh in 1990 (cum laude) and, after a post-doctoral stay at the DKFZ in Heidelberg (with Prof. Dr G Hammerling and Dr Frank Momburg) started my group at the Netherlands Cancer Institute in 1994. I continued studying the cell biology of MHC class I and MHC class II molecules. I and my group determined amongst others the specificity of the peptide transporter TAP, defined allelic differences in the cell biology of MHC class I molecules, co-founded the DRiPs (with Jon Yewdell), identified the activity of cytosolic peptidases and identified gap junctions as a mode for intercellular peptide transfer (for cross-presentation). For MHC class II molecules, we further defined the so-called MIIC, defined the details of control of MIIC mobility, defined the role of PI3 kinases in MIIC formation, identified the function of HLA-DO and determined the location of interaction between MHC class II and HLA-DM molecules.
We realized the power of GFP early in 1995, and have developed fluorescent techniques to approach so-called single cell biochemistry. We have developed various systems using combinations of cell biology, chemistry and biophysics to visualize biochemical reactions in living cells. These include the dynamics of proteasomes, the peptide transporter TAP, peptides, ubiquitin and MHC class I and MHC class II molecules. These have uncovered many new aspects of the process of antigen presentation by MHC class I and MHC class II molecules. We are currently combining these techniques with large scale screening approaches to identify new proteins and pathways involved in these processes. Below, you can find the lab members presenting themselves and their work. We hope you enjoy it!
Biographic sketch
Jacques Neefjes has a professor chair at the University of Leiden. He is currently deputy director research of the NKI. He was elected EMBO member in 2006. He has obtained the annual Golden Medal award from the Dutch Chemical Society (1996) and the Antoni van Leeuwenhoek award for his work. Jacques Neefjes is married with Andra Borst and has three kids; Els, Cor and Anna.
Selected publications (out of 170)
For a full overview of all publications consult PubMed
Neefjes, J.J., Stollorz,V., Peters,P.J., Geuze,H.J. and Ploegh,H.L. (1990c). The biosynthetic pathway of MHC class II but not class I molecules intersects the endocytic route. Cell 61, 171-183.
Peters,P.J., Neefjes, J.J., Oorschot,V., Ploegh,H.L. and Geuze,H.J. (1991). Segregation of MHC class II molecules from MHC class I molecules in the Golgi complex for transport to lysosomal compartments [see comments]. Nature 349, 669-676.
Neefjes, J.J., Momburg,F. and Hammerling,G.J. (1993c). Selective and ATP-dependent translocation of peptides by the MHC- encoded transporter. Science 261, 769-771.
Momburg,F., Roelse,J., Howard,J.C., Butcher,G.W., Hammerling,G.J. and Neefjes, J.J. (1994d). Selectivity of MHC-encoded peptide transporters from human, mouse and rat. Nature 367, 648-651.
Roelse,J., Gromme,M., Momburg,F., Hammerling,G. and Neefjes, J. (1994). Trimming of TAP-translocated peptides in the endoplasmic reticulum and in the cytosol during recycling. J Exp Med 180, 1591-1597.
Wubbolts,R., Fernandez-Borja,M., Oomen,L., Verwoerd,D., Janssen,H., Calafat,J., Tulp,A., Dusseljee,S. and Neefjes, J. (1996). Direct vesicular transport of MHC class II molecules from lysosomal structures to the cell surface. J Cell Biol 135, 611-622.
Fernandez-Borja,M., Wubbolts,R., Calafat,J., Janssen,H., Divecha,N., Dusseljee,S. and Neefjes, J. (1999). Multivesicular body morphogenesis requires phosphatidyl-inositol 3-kinase activity. Curr Biol 9, 55-58.
Reits,E.A., Vos,J.C., Gromme,M. and Neefjes, J. (2000). The major substrates for TAP in vivo are derived from newly synthesized proteins. Nature 404, 774-778.
Jordens,I., Fernandez-Borja,M., Marsman,M., Dusseljee,S., Janssen,L., Calafat,J., Janssen,H., Wubbolts,R. and Neefjes, J. (2001). The Rab7 effector protein RILP controls lysosomal transport by inducing the recruitment of dynein-dynactin motors. Curr Biol 11, 1680-1685.
Reits,E.A. and Neefjes, J.J. (2001). From fixed to FRAP: measuring protein mobility and activity in living cells. Nat. Cell Biol. 3, 145-147.
Reits,E., Griekspoor,A., Neijssen,J., Groothuis,T., Jalink,K., van Veelen,P., Janssen,H., Calafat,J., Drijfhout,J.W.JJ and Neefjes, J. (2003). Peptide diffusion, protection and degradation in nuclear and cytoplasmic compartments before antigen presentation by MHC class I. Immunity 18, 97-108.
Reits, E., Neijssen, J., Herberts, C., Benckhuijsen, W., Janssen, L., Drijfhout, J.W. and Neefjes, J. (2004). A major role for TPPII in trimming proteasomal degradation products for MHC class I antigen presentation. Immunity 20, 495-506.
Neijssen, C. Herberts, J. W. Drijfhout, E. Reits, L. Janssen and J. Neefjes. (2005) Cross-presentation by intercellular peptide transfer through gap junctions. Nature 434 (7029):83-88.
Reits, E.A., Hodge, J.W., Herberts, C.A., Groothuis, T.A., Chakraborty, M., Wansley, E.K., Capmhausen, K., Luiten, R.M., deRu, A.H., Neijssen, J., Griekspoor, A., Mesman, E., Verreck, F.A., Spits, H., Schlom, J., van Veelen, P., and Neefjes, J. (2006) Radiation modulates the peptide repertoire, enhances MHC class I expression, and induces successful antitumor immunotherapy. J. Exp. Med., 203(5), 1259-71.
Elliott, T. and Neefjes, J. (2006) The complex route to MHC class I-peptide complexes. Cell 127: 249-51.
Co-workers
Gosia Garstka PhD Post-doc
Coen Kuijl PhD Post-doc
Victoria Menendez PhD Post-doc
Charlotte Sadaka Post-doc
Tiziana Scanu PhD Post-doc
Marlieke Jongsma MSC PhD student
Baoxu Pang MSc PhD student
Petra Paul MSc PhD student
Izhar Salomon MSc PhD student
Tineke van den Hoorn MSc PhD student
Rik van der Kant MSc PhD student
Sjoerd van Deventer MSc PhD student
Ruud Wijdeven MSc PhD student
Lennert Janssen BSc Technical staff