title: Loss of HIV-1-derived cytotoxic T lymphocyte epitopes restricted by protective HLA-B alleles during the HIV-1 epidemic.
abstract: OBJECTIVE
  HIV-1 is known to adapt to the human immune system, leading to accumulation of escape mutations during the course of infection within an individual. Cross-sectional studies have shown an inverse correlation between the prevalence of human leukocyte antigen (HLA) alleles in a population and the number of cytotoxic T lymphocyte (CTL) escape mutations in epitopes restricted by those HLA alleles. Recently, it was demonstrated that at a population level HIV-1 is adapting to the humoral immune response, which is reflected in an increase in resistance to neutralizing antibodies over time. Here we investigated whether adaptations to cellular immunity have also accumulated during the epidemic.
  
  
  METHODS
  We compared the number of CTL epitopes in HIV-1 strains isolated from individuals who seroconverted at the beginning of the HIV-1 epidemic and from individuals who seroconverted in recent calendar time.
  
  
  RESULTS
  The number of CTL epitopes in HIV-1 variants restricted by the most common HLA alleles in the population did not change significantly during the epidemic. In contrast, we found a significant loss of CTL epitopes restricted by HLA-B alleles associated with a low relative hazard of HIV-1 disease progression during the epidemic. Such a loss was not observed for CTL epitopes restricted by HLA-A alleles.
  
  
  CONCLUSIONS
  Despite the large degree of HLA polymorphism, HIV-1 has accumulated adaptations to CTL responses within 20 years of the epidemic. The fact that such adaptations are driven by the HLA-B molecules that provide best protection against HIV-1 disease progression has important implications for our understanding of HIV evolution.
authors.affiliation: aDepartment of Immunology, University Medical Center Utrecht, The Netherlands.
authors.forename: Ingrid M M
authors.initials: IM
authors.lastname: Schellens
authors.forename: Marjon
authors.initials: M
authors.lastname: Navis
authors.forename: Hanneke W M
authors.initials: HW
authors.lastname: van Deutekom
authors.forename: Brigitte
authors.initials: B
authors.lastname: Boeser-Nunnink
authors.forename: Ben
authors.initials: B
authors.lastname: Berkhout
authors.forename: Neeltje
authors.initials: N
authors.lastname: Kootstra
authors.forename: Frank
authors.initials: F
authors.lastname: Miedema
authors.forename: Can
authors.initials: C
authors.lastname: Keşmir
authors.forename: Hanneke
authors.initials: H
authors.lastname: Schuitemaker
authors.forename: Debbie
authors.initials: D
authors.lastname: van Baarle
authors.forename: José A M
authors.initials: JA
authors.lastname: Borghans
mesh_terms: D000328:Adult; D003430:Cross-Sectional Studies; D018450:Disease Progression; D058872:Epidemics; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D019143:Evolution, Molecular; D005260:Female; D015658:HIV Infections / Q000453:epidemiology* / Q000276:immunology*; D006679:HIV Seropositivity / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D015235:HLA-B Antigens / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010802:Phylogeny; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte; D015235:HLA-B Antigens