Press release

 

A step closer to new generation vaccines

Paris, February 26, 2003

 


Researchers have demonstrated a new activity of an intracellular enzyme in the generation of an HIV epitope (an epitope is a good target for the lymphocytes stimulated by vaccines). What is original with this finding is that it unseats the proteasome, the intracellular enzymatic complex which, until now, seemed irreplaceable to make one of the enzymatic cuts producing these epitopes. The team of the Cochin Institute(1) directed by CNRS researcher Anne Hosmalin conducted this research as part of an international collaboration. Their findings, which were published in the April 2003 issue of the journal Nature Immunology(2), may have an impact on the development of new generation vaccines against viruses and tumors.


Lymphocytes in the immune system know how to recognize viral proteins and cancer cells in order to prevent their proliferation. Vaccination, whether preventive or therapeutic, stimulates the responses of these lymphocytes. New generation vaccines contain epitopes, fragments of viral proteins or tumors that are recognized by T lymphocytes. Such fragments are not infectious. When CD8 T lymphocytes recognize the epitopes, they destroy the infected or cancerous cells by producing anti-viral or anti-cancer factors, such as gamma interferon.

Understanding the mechanisms involved in the generation of epitopes makes it possible to characterize the epitopes that are useful for the activation of T lymphocytes in the composition of vaccines. For the scientists, an intracellular enzyme appeared to be required to generatef CD8 T cell epitopes: the proteasome. Their research demonstrated an example where the activity of the proteasome is replaced by that of another intracellular enzyme called TPP II (Tripeptidyl peptidase two). If confirmed for other epitopes, the new role of TPP II should be taken into account for the development of new generation vaccines against viruses and tumors.

These findings were obtained using human dendritic(3) cells and a dominant HIV epitope contained in the Nef protein that is recognized by CD8 lymphocytes. The Nef protein is a good target for vaccination against HIV, as it is expressed early in the viral cycle. Following digestion by the cell into peptides, the epitopes of this protein can be recognized by CD8+ T lymphocytes before the virus produces structural proteins. Thus, infected cells can be destroyed and viral replication can be inhibited before viruses are produced. .

References:
An essential role for tripeptidyl peptidase in the generation of an MHC class I epitope, Nature Immunology, April 2003.
Ulrike Seifert (1), Concepción Marañón (2), Ayelet Shmueli(3), Jean-François Desoutter (2), Lisa Wesoloski(1), Katharina Janek(1), Peter Henklein (1), Susanne Diescher (4), Muriel Andrieu (2), Henri de la Salle (5), Toni Weinschenk (6), Hansjörg Schild (6), Diego Laderach (7), Anne Galy (7), Gaby Haas (4), Peter-M. Kloetzel(1), Yuval Reiss (3) et Anne Hosmalin (2).

(1) Institut für Biochemie-Charité, Medical Faculty of the Humboldt-University Berlin, Berlin, Germany;
(2) Institut Cochin, Département d´Immunologie, U Inserm 567, CNRS UMR 8104, IFR Alfred Jost, Paris, France;
(3) Department of Biochemistry, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel;
(4) Max Planck Institut für Infektionsbiologie, Department of Molecular Biology, Berlin, Germany;
(5) INSERM EP99-08, EFS-Alsace, 676065 Strasbourg, France;
(6) Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen, Germany;
(7) INSERM U362, Institut Gustave Roussy, Villejuif and Généthon, Evry, France.


(1) The Cochin Institute is a research unit run jointly by the CNRS (UMR 8104), the INSERM (U567) and the Université René Descartes Paris 5 (IFR Alfred Jost).
(2) The article was posted on line February 24, 2003 at: http://www.nature.com/ni
(3) Dendritic cells play a very important role in the immune system: by presenting epitopes to T lymphocytes, they stimulate T lymphocyte immune responses.


Researcher contact:
Anne Hosmalin
Tel : +33 1 40 51 65 06
hosmalin@cochin.inserm.fr
anne.hosmalin@wanadoo.fr

Cochin Institute, communications contact:
Marie-Pascale Corneloup-Brossollet
Tel : +33 1 40 51 64 85
corneloup@cochin.inserm.fr

Press contact :
Magali Sarazin
Tel : +33 1 44 96 46 06
e-mail : magali.sarazin@cnrs-dir.fr

CNRS Life Sciences Department, communications contact:
Françoise Tristani
Tel : +33 1 44 96 40 26
francoise.tristani@cnrs-dir.fr