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Structural and functional analysis of virus specific TCR-pMHC recognition

Obiettivo

The proposed research plans to understand the relationship between structural requirements for TCR/peptide/MHC interactions and their influence on TCR repertoire diversity given it has been reported that increased T cell repertoire diversity correlates with increased resistance to viral infection. While the structural characteristics of TCR/peptide/MHC interactions can be elucidated, a large question that remains is how these factors influence the function of virus-specific CTL generated after infection.

This proposal aims to first study the molecular interactions that define specific TCR recognition of both DbNP366 and DbPA224 complexes (respiratory infection of C57BL/6J (H-2b) mice with influenza A viruses induces CD8+ T cell responses specific for epitopes derived from nucleoprotein amino acid 366-374 and acidic polymerase amino acid 224-233 with structural and functional differences). The second aim utilises a retroviral transduction system to ectopically express TCRs of known specificity. This will facilitate the analysis of functional characteristics of these transduced T cells after infection. In this way, this proposal will link the structural aspects of TCR recognition of peptide/MHC complexes and the in vivo consequences these interactions have on the responding T cell repertoire. These studies will provide a rationale for vaccine design human viral pathogens such as HIV, Hepatitis C and Influenza A virus.

Invito a presentare proposte

FP6-2005-MOBILITY-6
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Coordinatore

INSTITUT NATIONAL DE LA SANTÃ'© ET DE LA RECHERCHE MÃ'©DICALE
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Indirizzo
63 QUAI MAGELLAN HALL B
32116 NANTES
Francia

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