title: Escape from highly effective public CD8+ T-cell clonotypes by HIV.
abstract: Mapping the precise determinants of T-cell efficacy against viruses in humans is a public health priority with crucial implications for vaccine design. To inform this effort, we performed a comprehensive analysis of the effective CD8(+) T-cell clonotypes that constitute responses specific for the HIV p24 Gag-derived KK10 epitope (KRWIILGLNK; residues 263-272) restricted by HLA-B*2705, which are known to confer superior control of viral replication in HIV-infected individuals. Particular KK10-specific CD8(+) T-cell clonotypes, characterized by TRBV4-3/TRBJ1-3 gene rearrangements, were found to be preferentially selected in vivo and shared between individuals. These "public" clonotypes exhibit high levels of TCR avidity and Ag sensitivity, which impart functional advantages and enable effective suppression of HIV replication. The early L(268)M mutation at position 6 of the KK10 epitope enables the virus to avoid recognition by these highly effective CD8(+) T-cell clonotypes. However, alternative clonotypes with variant reactivity provide flexibility within the overall KK10-specific response. These findings provide refined mechanistic insights into the workings of an effective CD8(+) T-cell response against HIV.
authors: Inserm UMR S 945, Infections and Immunity, Université Pierre et Marie Curie-Paris 6, Hôpital Pitié-Salpêtrière, Paris, France.
authors: Maria Candela
authors: MC
authors: Iglesias
authors: Jorge R
authors: JR
authors: Almeida
authors: Solène
authors: S
authors: Fastenackels
authors: David J
authors: DJ
authors: van Bockel
authors: Masao
authors: M
authors: Hashimoto
authors: Vanessa
authors: V
authors: Venturi
authors: Emma
authors: E
authors: Gostick
authors: Alejandra
authors: A
authors: Urrutia
authors: Linda
authors: L
authors: Wooldridge
authors: Mathew
authors: M
authors: Clement
authors: Stéphanie
authors: S
authors: Gras
authors: Pascal G
authors: PG
authors: Wilmann
authors: Brigitte
authors: B
authors: Autran
authors: Arnaud
authors: A
authors: Moris
authors: Jamie
authors: J
authors: Rossjohn
authors: Miles P
authors: MP
authors: Davenport
authors: Masafumi
authors: M
authors: Takiguchi
authors: Christian
authors: C
authors: Brander
authors: Daniel C
authors: DC
authors: Douek
authors: Anthony D
authors: AD
authors: Kelleher
authors: David A
authors: DA
authors: Price
authors: Victor
authors: V
authors: Appay
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D015331:Cohort Studies; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D016655:HIV Core Protein p24 / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000235:genetics / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity / Q000502:physiology; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D014779:Virus Replication / Q000276:immunology
chemical_list: D000939:Epitopes; D016655:HIV Core Protein p24; C514799:p24 protein, Human Immunodeficiency Virus Type 1