title: Differential characteristics of cytotoxic T lymphocytes restricted by the protective HLA alleles B*27 and B*57 in HIV-1 infection.
abstract: OBJECTIVE
  HLA-B*27 and B*57 are associated with relatively slow progression to AIDS. Mechanisms held responsible for this protective effect include the immunodominance and high magnitude, breadth, and affinity of the cytotoxic T lymphocytes (CTL) response restricted by these HLA molecules, as well as superior maintenance of CTL responses during HIV-1 disease progression.
  
  
  METHODS
  We examined CTL responses from HIV-1-infected individuals restricted through protective and nonprotective HLA alleles within the same host, thereby excluding any effects of slow or rapid progression on the CTL response.
  
  
  RESULTS
  We found that neither immunodominance, nor high magnitude and breadth, nor affinity of the CTL response are general mechanisms of protection against disease progression. HLA-B*57-restricted CTL responses were of exceptionally high affinity and dominated the HLA-A*02-restricted CTL response in individuals coexpressing these HLA alleles. In contrast, HLA-B*27-restricted CTL responses were not of particularly high affinity and did not dominate the response in individuals coexpressing HLA-B*27 and HLA-A*02. Instead, in individuals expressing HLA-B*27, the CTL response restricted by nonprotective HLA alleles was significantly higher and broader, and of higher affinity than in individuals expressing these alleles without HLA-B*27. Although HLA-B*27 and B*57 are thought to target the most conserved parts of HIV, during disease progression, CTL responses restricted by HLA-B*27 and B*57 were lost at least as fast as CTL responses restricted by HLA-A*02.
  
  
  CONCLUSIONS
  Our data show that many of the mechanisms of CTL that are generally held responsible for slowing down HIV-1 disease progression hold for HLA-B*57 but do not hold for HLA-B*27.
authors.affiliation: Departments of *Immunology; †Internal Medicine and Infectious Diseases, University Medical Center Utrecht, Utrecht, The Netherlands; and ‡Department of Experimental Immunology, Academic Medical Center, Amsterdam, The Netherlands (Schellens, Nanlohy, and van Baarle is now with Center for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands; Coffeng is now with Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USA).
authors.forename: Ingrid M M
authors.initials: IM
authors.lastname: Schellens
authors.forename: Hilde B
authors.initials: HB
authors.lastname: Spits
authors.forename: Marjon
authors.initials: M
authors.lastname: Navis
authors.forename: Geertje H A
authors.initials: GH
authors.lastname: Westerlaken
authors.forename: Nening M
authors.initials: NM
authors.lastname: Nanlohy
authors.forename: Luc E
authors.initials: LE
authors.lastname: Coffeng
authors.forename: Neeltje
authors.initials: N
authors.lastname: Kootstra
authors.forename: Frank
authors.initials: F
authors.lastname: Miedema
authors.forename: Hanneke
authors.initials: H
authors.lastname: Schuitemaker
authors.forename: José A M
authors.initials: JA
authors.lastname: Borghans
authors.forename: Debbie
authors.initials: D
authors.lastname: van Baarle
mesh_terms: D000328:Adult; D015331:Cohort Studies; D018450:Disease Progression; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D015234:HLA-A Antigens / Q000235:genetics; D015235:HLA-B Antigens / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; D015235:HLA-B Antigens