title: Definition of the viral targets of protective HIV-1-specific T cell responses.
abstract: BACKGROUND
  The efficacy of the CTL component of a future HIV-1 vaccine will depend on the induction of responses with the most potent antiviral activity and broad HLA class I restriction. However, current HIV vaccine designs are largely based on viral sequence alignments only, not incorporating experimental data on T cell function and specificity.
  
  
  METHODS
  Here, 950 untreated HIV-1 clade B or -C infected individuals were tested for responses to sets of 410 overlapping peptides (OLP) spanning the entire HIV-1 proteome. For each OLP, a "protective ratio" (PR) was calculated as the ratio of median viral loads (VL) between OLP non-responders and responders.
  
  
  RESULTS
  For both clades, there was a negative relationship between the PR and the entropy of the OLP sequence. There was also a significant additive effect of multiple responses to beneficial OLP. Responses to beneficial OLP were of significantly higher functional avidity than responses to non-beneficial OLP. They also had superior in-vitro antiviral activities and, importantly, were at least as predictive of individuals' viral loads than their HLA class I genotypes.
  
  
  CONCLUSIONS
  The data thus identify immunogen sequence candidates for HIV and provide an approach for T cell immunogen design applicable to other viral infections.
authors.affiliation: Irsicaixa AIDS Research Institute-HIVACAT, Badalona, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Mothe
authors.forename: Anuska
authors.initials: A
authors.lastname: Llano
authors.forename: Javier
authors.initials: J
authors.lastname: Ibarrondo
authors.forename: Marcus
authors.initials: M
authors.lastname: Daniels
authors.forename: Cristina
authors.initials: C
authors.lastname: Miranda
authors.forename: Jennifer
authors.initials: J
authors.lastname: Zamarreño
authors.forename: Vanessa
authors.initials: V
authors.lastname: Bach
authors.forename: Rosario
authors.initials: R
authors.lastname: Zuniga
authors.forename: Susana
authors.initials: S
authors.lastname: Pérez-Álvarez
authors.forename: Christoph T
authors.initials: CT
authors.lastname: Berger
authors.forename: Maria C
authors.initials: MC
authors.lastname: Puertas
authors.forename: Javier
authors.initials: J
authors.lastname: Martinez-Picado
authors.forename: Morgane
authors.initials: M
authors.lastname: Rolland
authors.forename: Marilu
authors.initials: M
authors.lastname: Farfan
authors.forename: James J
authors.initials: JJ
authors.lastname: Szinger
authors.forename: William H
authors.initials: WH
authors.lastname: Hildebrand
authors.forename: Otto O
authors.initials: OO
authors.lastname: Yang
authors.forename: Victor
authors.initials: V
authors.lastname: Sanchez-Merino
authors.forename: Chanson J
authors.initials: CJ
authors.lastname: Brumme
authors.forename: Zabrina L
authors.initials: ZL
authors.lastname: Brumme
authors.forename: David
authors.initials: D
authors.lastname: Heckerman
authors.forename: Todd M
authors.initials: TM
authors.lastname: Allen
authors.forename: James I
authors.initials: JI
authors.lastname: Mullins
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Gómez
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Goulder
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
authors.forename: Jose M
authors.initials: JM
authors.lastname: Gatell
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Clotet
authors.forename: Bette T
authors.initials: BT
authors.lastname: Korber
authors.forename: Jorge
authors.initials: J
authors.lastname: Sanchez
authors.forename: Christian
authors.initials: C
authors.lastname: Brander
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D015331:Cohort Studies; D017124:Conserved Sequence / Q000235:genetics; D018740:Genetic Heterogeneity; D015658:HIV Infections / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D008297:Male; D015999:Multivariate Analysis; D010455:Peptides / Q000276:immunology; D010568:Peru; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D019562:Viral Load / Q000276:immunology; D014779:Virus Replication / Q000276:immunology; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000276:immunology
chemical_list: D015395:Histocompatibility Antigens Class I; D010455:Peptides; D054301:gag Gene Products, Human Immunodeficiency Virus