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B cell and antibody immunodominance in antiviral immune responses

Davide Angeletti

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Seasonal influenza causes significant morbidity and mortality every year, with the possibility of global pandemic outbreaks. Current vaccines provide reasonable protection against circulating viruses but require yearly reformulation. Therefore, there is an urgent need to develop a vaccine that could provide long term immunity to the virus. Our work aims at defining the basic immunological mechanisms of antibody and B cell responses as an essential step towards an effective universal vaccination.

In peripheral lymphnodes, structures called germinal centers emerge after a challenge by a foreign antigen. These structures are primarily composed of B cells that bound with sufficient avidity to the antigen. In the germinal centers, B cells proliferate, increase their avidity for the antigen and finally differentiate into antibody secreting plasma cells.


The picture shows germinal centers (in green) in a mediastinal lymphnode section after influenza infection. Image credit: Heather Hickman (NIH)

 

But not all B cells are made equal: there are major differences between B cells of different specificities, even for distinct parts of the same molecule. Which B cells can enter the germinal center? which can proliferate? and which can differentiate? These phenomena are regulated by immunodominance. Immunodominance is the phenomenon of unequal immunogenicity between competing antigens or epitopes on the same antigen. In the group we use influenza A virus surface protein, hemagglutinin, as a model to gain a more complete understanding of the rules that govern immunodominance, and ways to manipulate it.

Projects in our group focus on different aspects of immunodominance and are aimed at defining its basic mechanisms in order to manipulate immunodominance and direct antibody responses towards conserved epitopes. We combine in vivo and in vitro studies, using a range of immunological techniques, multicolor flow cytometry and single cell sequencing in order to address these questions.

Sidansvarig: Dan Baeckström|Sidan uppdaterades: 2018-08-23
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