Sequence flexibility of the immunodominant HLA A*0201 restricted ppUL83 CD8 T-cell epitope of human cytomegalovirus

Jakub Kopycinski (1) , Mohamad Osman (1) , Paul Griffiths (1) , Vincent Clive Emery (2)

1 Infection
2 Infection

The cytomegalovirus ppUL83 protein contains an immunodominant A*0201 restricted epitope between residues 495-503. We investigated the tolerance of this epitope to sequence variation in the context of peptide binding to HLA A*0201 and the ability to induce an Interferon (IFN) gamma response through engagement with the T-cell receptor (TCR). The majority of mutations investigated resulted in a decrease in the production of IFN gamma indicating that if such variants occurred in vivo they would not be recognised by CD8 T-cell clones specific for the wild type epitope. The mechanistic basis for the majority of the mutant peptides was their failure to bind and stabilise class I HLA cell surface expression. However, one peptide with a mutation at the P5 position (cysteine to methionine) resulted in a significant enhanced binding to HLA A*0201 and also an increase in cell surface expression over the wild type peptide but was unable to engage with the CD8 TCR and trigger interferon gamma production. This peptide acted as a competitive inhibitor of the wild type peptide but could not fully inhibit IFN gamma production by the latter. We subsequently investigated whether mutations of the HLA A*0201 epitope were evident in immunocompromised patients experiencing either rapid exponential or persistent cytomegalovirus replication.

Mots clés: Medicine

Jakub Kopycinski, Mohamad Osman, Paul Griffiths, Vincent Clive Emery. Sequence flexibility of the immunodominant HLA A*0201 restricted ppUL83 CD8 T-cell epitope of human cytomegalovirus. Journal of Medical Virology, 2009, 82 (1), pp.94. ⟨10.1002/jmv.21668⟩. ⟨hal-00541151⟩