title: HIV-1-Specific CD8 T Cells Exhibit Limited Cross-Reactivity during Acute Infection.
abstract: Prior work has demonstrated that HIV-1-specific CD8 T cells can cross-recognize variant epitopes. However, most of these studies were performed in the context of chronic infection, where the presence of viral quasispecies makes it difficult to ascertain the true nature of the original antigenic stimulus. To overcome this limitation, we evaluated the extent of CD8 T cell cross-reactivity in patients with acute HIV-1 clade B infection. In each case, we determined the transmitted founder virus sequence to identify the autologous epitopes restricted by individual HLA class I molecules. Our data show that cross-reactive CD8 T cells are infrequent during the acute phase of HIV-1 infection. Moreover, in the uncommon instances where cross-reactive responses were detected, the variant epitopes were poorly recognized in cytotoxicity assays. Molecular analysis revealed that similar antigenic structures could be cross-recognized by identical CD8 T cell clonotypes mobilized in vivo, yet even subtle differences in a single TCR-accessible peptide residue were sufficient to disrupt variant-specific reactivity. These findings demonstrate that CD8 T cells are highly specific for autologous epitopes during acute HIV-1 infection. Polyvalent vaccines may therefore be required to provide optimal immune cover against this genetically labile pathogen.
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294;
authors.forename: Victor Y
authors.initials: VY
authors.lastname: Du
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294;
authors.forename: Anju
authors.identifier: http://orcid.org/0000-0003-1880-4093
authors.initials: A
authors.lastname: Bansal
authors.affiliation: Microsoft Research, Redmond, WA 98052;
authors.forename: Jonathan
authors.identifier: http://orcid.org/0000-0001-6618-3653
authors.initials: J
authors.lastname: Carlson
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294;
authors.forename: Jesus F
authors.identifier: http://orcid.org/0000-0003-4626-6448
authors.initials: JF
authors.lastname: Salazar-Gonzalez
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294;
authors.forename: Maria G
authors.identifier: http://orcid.org/0000-0003-0823-7697
authors.initials: MG
authors.lastname: Salazar
authors.affiliation: Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff CF14 4XN, United Kingdom;
authors.forename: Kristin
authors.identifier: http://orcid.org/0000-0002-9856-2938
authors.initials: K
authors.lastname: Ladell
authors.affiliation: Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia; Australian Research Council Centre of Excellence for Advanced Molecular Imaging, Monash University, Clayton, Victoria 3800, Australia;
authors.forename: Stephanie
authors.identifier: http://orcid.org/0000-0001-7416-038X
authors.initials: S
authors.lastname: Gras
authors.affiliation: Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia;
authors.forename: Tracy M
authors.initials: TM
authors.lastname: Josephs
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294;
authors.forename: Sonya L
authors.identifier: http://orcid.org/0000-0002-3826-0954
authors.initials: SL
authors.lastname: Heath
authors.affiliation: Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff CF14 4XN, United Kingdom; Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and.
authors.forename: David A
authors.initials: DA
authors.lastname: Price
authors.affiliation: Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff CF14 4XN, United Kingdom; Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia; Australian Research Council Centre of Excellence for Advanced Molecular Imaging, Monash University, Clayton, Victoria 3800, Australia;
authors.forename: Jamie
authors.initials: J
authors.lastname: Rossjohn
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30329.
authors.forename: Eric
authors.identifier: http://orcid.org/0000-0002-4273-8631
authors.initials: E
authors.lastname: Hunter
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294; paulg@uab.edu.
authors.forename: Paul A
authors.identifier: http://orcid.org/0000-0001-8441-5737
authors.initials: PA
authors.lastname: Goepfert
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D003429:Cross Reactions / Q000276:immunology*; D018360:Crystallography, X-Ray; D018984:Epitopes, T-Lymphocyte / Q000276:immunology* / Q000648:ultrastructure; D015658:HIV Infections / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000145:classification / Q000276:immunology*; D015796:HLA-B27 Antigen / Q000276:immunology / Q000648:ultrastructure; D015793:HLA-B7 Antigen / Q000276:immunology* / Q000648:ultrastructure; D006801:Humans
chemical_list: D018984:Epitopes, T-Lymphocyte; C477444:HLA-B*07:02 antigen; C464936:HLA-B*27:05 antigen; D015796:HLA-B27 Antigen; D015793:HLA-B7 Antigen