Determinants of virus specific CD8+ T cell hierarchies.
Grant number: 454595 | Funding period: 2007 - 2009
The CD8+, or killer , T lymphocytes (white blood cells) are the hit men of immunity, recirculating continually around the body to eliminate other cells that are dangerous because they are cancerous or infected with a virus. A major difficulty is that killer T cells also exert selective pressures that cause viruses and tumours to mutate and thus avoid immune control. This is a particularly serious problem for RNA viruses that readily mutate as they divide. These include the human immunodeficiency virus (HIV) that causes AIDS and, while the mutations that are most important with influenza viruses are those that modify viral surface proteins recognized by antibodies, such T cell escape mutants ..View full description
Related publications (9)
Effect of MHC Class I Diversification on Influenza Epitope-Specific CD8( ) T Cell Precursor Frequency and Subsequent Effector Function
E Bridie Day, Kim L Charlton, Nicole L La Gruta, Peter C Doherty, Stephen J Turner
Earlier studies of influenza-specific CD8(+) T cell immunodominance hierarchies indicated that expression of the H2K(k) MHC class ..
Memory precursor phenotype of CD8( ) T cells reflects early antigenic experience rather than memory numbers in a model of localized acute influenza infection
Hayley A Croom, Alice E Denton, Sophie A Valkenburg, Natasha G Swan, Matthew R Olson, Stephen J Turner, Peter C Doherty, Katherine Kedzierska
The mechanistic basis of memory T-cell development is poorly defined. Phenotypic markers that define precursors at effector stages..
Influenza Epitope-Specific CD8( ) T Cell Avidity, but Not Cytokine Polyfunctionality, Can Be Determined by TCR beta Clonotype
Jessica M Moffat, Andreas Handel, Peter C Doherty, Stephen J Turner, Paul G Thomas, Nicole L La Gruta
Cytokine polyfunctionality has recently emerged as a correlate of effective CTL immunity to viruses and tumors. Although the deter..
Fixing an irrelevant TCR alpha chain reveals the importance of TCR beta diversity for optimal TCR alpha beta pairing and function of virus-specific CD8( ) T cells
Sophie A Valkenburg, E Bridie Day, Natasha G Swan, Hayley A Croom, Francis R Carbone, Peter C Doherty, Stephen J Turner, Katherine Kedzierska
TCR repertoire diversity can influence the efficacy of CD8(+) T-cell populations, with greater breadth eliciting better protection..
Protective Efficacy of Cross-Reactive CD8( ) T Cells Recognising Mutant Viral Epitopes Depends on Peptide-MHC-I Structural Interactions and T Cell Activation Threshold
Sophie A Valkenburg, Stephanie Gras, Carole Guillonneau, Nicole L La Gruta, Paul G Thomas, Anthony W Purcell, Jamie Rossjohn, Peter C Doherty, Stephen J Turner, Katherine Kedzierska
Emergence of a new influenza strain leads to a rapid global spread of the virus due to minimal antibody immunity. Pre-existing CD8..
Primary CTL response magnitude in mice is determined by the extent of naive T cell recruitment and subsequent clonal expansion
Nicole L La Gruta, William T Rothwell, Tania Cukalac, Natasha G Swan, Sophie A Valkenburg, Katherine Kedzierska, Paul G Thomas, Peter C Doherty, Stephen J Turner
CD8+ T cell responses to viral infection are characterized by the emergence of dominant and subdominant CTL populations. The immun..
Combined NKT cell activation and influenza virus vaccination boosts memory CTL generation and protective immunity
Carole Guillonneau, Justine D Mintern, Francois-Xavier Hubert, Aeron C Hurt, Gurdyal S Besra, Steven Porcelli, Ian G Barr, Peter C Doherty, Dale I Godfrey, Stephen J Turner
Current influenza A virus vaccines do not generate significant immunity against serologically distinct influenza A virus subtypes ..
Complete modification of TCR specificity and repertoire selection does not perturb a CD8( ) T cell immunodominance hierarchy
Katherine Kedzierska, Carole Guillonneau, Stephanie Gras, Lauren A Hatton, Richard Webby, Anthony W Purcell, Jamie Rossjohn, Peter C Doherty, Stephen J Turner
Understanding T cell immunodominance hierarchies is fundamental to the development of cellular-based vaccines and immunotherapy. A..
Epitope-specific TCR beta repertoire diversity imparts no functional advantage on the CD8( ) T cell response to cognate viral peptides
Nicole L La Gruta, Paul G Thomas, Andrew I Webb, Michelle A Dunstone, Tania Cukalac, Peter C Doherty, Anthony W Purcell, Jamie Rossjohn, Stephen J Turner
TCR repertoire diversity has been convincingly shown to facilitate responsiveness of CD8+ T cell populations to mutant virus pepti..