Epitopes described in "A molecular basis for the control of preimmune escape variants by HIV-specific CD8+ T cells."

Article Authors:Kristin Ladell; Masao Hashimoto; Maria Candela Iglesias; Pascal G Wilmann; James E McLaren; Stéphanie Gras; Takayuki Chikata; Nozomi Kuse; Solène Fastenackels; Emma Gostick; John S Bridgeman; Vanessa Venturi; Zaïna Aït Arkoub; Henri Agut; David J van Bockel; Jorge R Almeida; Daniel C Douek; Laurence Meyer; Alain Venet; Masafumi Takiguchi; Jamie Rossjohn; David A Price; Victor Appay
Article Title:A molecular basis for the control of preimmune escape variants by HIV-specific CD8+ T cells.
Reference Detail
Reference ID:1025721
Abstract:The capacity of the immune system to adapt to rapidly evolving viruses is a primary feature of effective immunity, yet its molecular basis is unclear. Here, we investigated protective HIV-1-specific CD8+ T cell responses directed against the immunodominant p24 Gag-derived epitope KK10 (KRWIILGLNK263-272) presented by human leukocyte antigen (HLA)-B∗2705. We found that cross-reactive CD8+ T cell clonotypes were mobilized to counter the rapid emergence of HIV-1 variants that can directly affect T cell receptor (TCR) recognition. These newly recruited clonotypes expressed TCRs that engaged wild-type and mutant KK10 antigens with similar affinities and almost identical docking modes, thereby accounting for their antiviral efficacy in HLA-B∗2705+ individuals. A protective CD8+ T cell repertoire therefore encompasses the capacity to control TCR-accessible mutations, ultimately driving the development of more complex viral escape variants that disrupt antigen presentation.
Reference Type:Literature
PubMed ID:23521884
Journal Volume:38
Article Pages:425-36
Journal ISSN:1074-7613
Article Chemical List:Epitopes, T-Lymphocyte;HIV Core Protein p24;HLA-B*27:05 antigen;HLA-B27 Antigen;Immunodominant Epitopes;Receptors, Antigen, T-Cell;p24 protein, Human Immunodeficiency Virus Type 1
Article MeSH List:Amino Acid Sequence; Antigen Presentation(immunology); CD8-Positive T-Lymphocytes(immunology; metabolism; virology); Clone Cells(immunology; metabolism; virology); Crystallography, X-Ray; Epitopes, T-Lymphocyte(chemistry; immunology; metabolism); HIV Core Protein p24(genetics; immunology; metabolism); HIV Infections(immunology; virology); HIV-1(genetics; immunology; metabolism); HLA-B27 Antigen(chemistry; immunology; metabolism); Humans; Immunodominant Epitopes(chemistry; immunology; metabolism); Models, Molecular; Molecular Sequence Data; Mutation; Protein Binding(immunology); Protein Structure, Tertiary; Receptors, Antigen, T-Cell(genetics; immunology; metabolism)
Curation Last Updated:2014-10-14 18:31:46