Friday, 15th December 2017
Cell Biology and Immunology
                   Viral Immunology

 

 

 grupo.400px

 


 

 

Margarita del Val

 

 ASciStaff

 

APublications

 

 

 

 

Research summary:

Viral Immunology Unit

Our field of interest is to study the mechanisms underlying the cellular immune response to viral infections, in order to gain knowledge useful for rationale vaccine development. For many strongly cytopathic infections, vaccines eliciting strong neutralizing antibody responses are the choice. However, there is a strong need for new stimulating strategies for vaccine design to fight chronic and less cytopathic infections, for which long-lasting and potent T-lymphocyte-mediated immune responses are essential.

 

 

 

 

 

Fig.300px

 

...............

------------

-------------

 ------

 

.....

......

 

 

 

We study the mechanisms of antigen processing and presentation by MHC class I molecules in virus-infected cells, which allow their elimination by CD8+ cytotoxic T lymphocytes, as well as in dendritic cells, which prime these lymphocytes. We study novel proteases that can process viral antigens Indeed, we have identified the trans-Golgi network proprotein convertase furin as a novel antigen processing enzyme of the secretory pathway, which can process all antigens tested so far. Furthermore, we have recently shown that viral antigens destroyed by proteasomes can be productively processed by tripeptidyl-peptidase II, another major house-keeping cytosolic protease. In addition, we and have shown that pro-apoptotic and pro-inflammatory caspases contribute to viral antigen processing in vitro and in vivo. In addition, we study novel routes of viral antigen presentation to CD8+ T lymphocytes, which take place in the secretory pathway and which are independent of TAP transporters. Extension of these studies to in vivo animal models of infection underscores the quantitative physiological relevance of the novel viral antigen processing pathways in vivo, and may also help explain why TAP-deficient humans control most pathogen infections.

Finally, we research into factors that contribute to an efficient and long-lasting CD8+ T lymphocyte memory response. Factors that promote strong effector primary responses appear to differ from those that warrant potent memory, and we are focusing on novel memory-promoting factors, by studying viral as well as parasite models of infection in vivo.


 

Relevant publications:

  • “N-ras couples antigen receptor signaling to Eomesodermin and to functional CD8+ T-cell memory but not to effector differentiation”. S. Iborra, M. Ramos, D. M. Arana, S. Lázaro, F. Aguilar, E. Santos, D. López, E. Fernández-Malavé, and M. Del Val. J. Exp. Med., 210, 1463-1479 (2013).
  • “Gene expression induced by Toll-like receptors in macrophages requires the transcription factor NFAT5”. M. Buxadé, G. Lunazzi, J. Minguillón, S. Iborra, R. Berga-Bolaños, M. Del Val, J. Aramburu and C. López-Rodríguez. J. Exp. Med., 209, 379-393. (2012).
  • “Need for tripeptidyl-peptidase II in MHC class I viral antigen processing when proteasomes are detrimental”. S. Guil, M. Rodríguez-Castro, F. Aguilar, E. M. Villasevil, L. C. Antón, and M. Del Val. J. Biol. Chem. 281, 39925-39934. (2006).
  • “Concerted peptide trimming by human ERAP1 and ERAP2 aminopeptidase complexes in the endoplasmic reticulum”. L. Saveanu, O. Carroll, V. Lindo, M. Del Val, D. López, Y. Lepelletier, F. Greer, L. Schomburg, D. Fruci, G. Niedermann, and P. M. van Endert. Nature Immunol., 6, 689-697 (2005).
  • "MHC class I viral antigen processing in the secretory pathway defined by the trans-Golgi network protease furin". B. C. Gil-Torregrosa, A. R. Castaño, and M. Del Val. J. Exp. Med., 188, 1105-1116 (1998).