Epitope length variants balance protective immune responses and viral escape in HIV-1 infection.

Autor:	Pymm P; Nuffield Department of Clinical Neurosciences, Division of Clinical Neurology, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Headley Way, Oxford OX3 9DS, UK; Walter and Eliza Hall Institute of Medical Research, University of Melbourne, 1G Royalparade, Parkville, VIC 3052, Australia., Tenzer S; Institute of Immunology, University Medical Center of the Johannes-Gutenberg University of Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany., Wee E; Nuffield Department of Clinical Neurosciences, Division of Clinical Neurology, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Headley Way, Oxford OX3 9DS, UK., Weimershaus M; Institut National de la Santé et de la Recherche Médicale, Unité 1151, Université Paris Descartes, Sorbonne Paris Cité, Hôpital Necker, 149 Rue de Severs, 75015 Paris, France; Centre National de la Recherche Scientifique, UMR8253, Université Paris Descartes, Sorbonne Paris Cité, Hôpital Necker, 149 Rue de Severs, 75015 Paris, France., Burgevin A; Institut National de la Santé et de la Recherche Médicale, Unité 1151, Université Paris Descartes, Sorbonne Paris Cité, Hôpital Necker, 149 Rue de Severs, 75015 Paris, France; Centre National de la Recherche Scientifique, UMR8253, Université Paris Descartes, Sorbonne Paris Cité, Hôpital Necker, 149 Rue de Severs, 75015 Paris, France., Kollnberger S; Division of Infection and Immunity, Cardiff University School of Medicine, University Hospital of Wales, Heath Park, CF14 4XN Cardiff, UK., Gerstoft J; Department of Infectious Diseases, Rigshospitalet, The National University Hospital, Blegdamsvej 9, 2100 Copenhagen, Denmark., Josephs TM; Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, 381 Royal Parade, Parkville, VIC 3052, Australia., Ladell K; Division of Infection and Immunity, Cardiff University School of Medicine, University Hospital of Wales, Heath Park, CF14 4XN Cardiff, UK., McLaren JE; Division of Infection and Immunity, Cardiff University School of Medicine, University Hospital of Wales, Heath Park, CF14 4XN Cardiff, UK., Appay V; Institut National de la Santé et de la Recherche Médicale, Unité 1135, Centre d'Immunologie et des Maladies Infectieuses, Sorbonne Université, Boulevard de l'Hopital, 75013 Paris, France; International Research Center of Medical Sciences, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto City 860-0811, Japan., Price DA; Division of Infection and Immunity, Cardiff University School of Medicine, University Hospital of Wales, Heath Park, CF14 4XN Cardiff, UK; Systems Immunity Research Institute, Cardiff University School of Medicine, University Hospital of Wales, Tenovus Building, CF14 4XN Cardiff, UK., Fugger L; Nuffield Department of Clinical Neurosciences, Division of Clinical Neurology, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Headley Way, Oxford OX3 9DS, UK; Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, OX3 9DS Oxford, UK., Bell JI; Office of the Regius Professor of Medicine, The Richard Doll Building, University of Oxford, Old Road Campus, OX3 7LF Oxford, UK., Schild H; Institute of Immunology, University Medical Center of the Johannes-Gutenberg University of Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany., van Endert P; Institut National de la Santé et de la Recherche Médicale, Unité 1151, Université Paris Descartes, Sorbonne Paris Cité, Hôpital Necker, 149 Rue de Severs, 75015 Paris, France; Centre National de la Recherche Scientifique, UMR8253, Université Paris Descartes, Sorbonne Paris Cité, Hôpital Necker, 149 Rue de Severs, 75015 Paris, France., Harkiolaki M; Structural Biology Group, Wellcome Trust Centre for Human Genetics, University of Oxford, Old Road Campus, OX3 7LF Oxford, UK; Diamond Light Source, Harwell Science and Innovation Campus, Fermi Avenue, OX11 0DE Didcot, UK., Iversen AKN; Nuffield Department of Clinical Neurosciences, Division of Clinical Neurology, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Headley Way, Oxford OX3 9DS, UK. Electronic address: astrid.iversen@ndcn.ox.ac.uk.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2022 Mar 01; Vol. 38 (9), pp. 110449.
DOI:	10.1016/j.celrep.2022.110449
Abstrakt:	Cytotoxic T lymphocyte (CTL) and natural killer (NK) cell responses to a single optimal 10-mer epitope (KK10) in the human immunodeficiency virus type-1 (HIV-1) protein p24Gag are associated with enhanced immune control in patients expressing human leukocyte antigen (HLA)-B ∗ 27:05. We find that proteasomal activity generates multiple length variants of KK10 (4-14 amino acids), which bind TAP and HLA-B ∗ 27:05. However, only epitope forms ≥8 amino acids evoke peptide length-specific and cross-reactive CTL responses. Structural analyses reveal that all epitope forms bind HLA-B ∗ 27:05 via a conserved N-terminal motif, and competition experiments show that the truncated epitope forms outcompete immunogenic epitope forms for binding to HLA-B ∗ 27:05. Common viral escape mutations abolish (L136M) or impair (R132K) production of KK10 and longer epitope forms. Peptide length influences how well the inhibitory NK cell receptor KIR3DL1 binds HLA-B ∗ 27:05 peptide complexes and how intraepitope mutations affect this interaction. These results identify a viral escape mechanism from CTL and NK responses based on differential antigen processing and peptide competition. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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