title: Immunological control of chronic HIV-1 infection: HLA-mediated immune function and viral evolution in adolescents.
abstract: BACKGROUND
  Differential protein targeting by HIV-specific CD8 T cells is associated with disparate plasma viral loads; however, it is unclear if the quality of these responses differs depending upon the specificity of the targeted epitopes.
  
  
  METHODS
  We examined HIV-specific CD8 T-cell responses in HIV-infected adolescents carrying either an HLA class I allele associated with a favorable prognosis (HLA-B*57) or an allele associated with usual disease progression (HLA-B*35 or HLA-B*53) using interferon-gamma ELISpot and ICS assays.
  
  
  RESULTS
  In an interferon-gamma ELISpot assay, p24 was the dominant protein targeted by B*57 carriers while responses to Nef dominated in B*35 or B*53 positive carriers. This differential protein targeting did not change during 4 years of follow-up. In these chronically infected adolescents, there were no significant differences in the quality of the immunodominant T-cell responses between the B*57 and B*35/B*53 carriers as measured by peptide avidity, degranulation, and immune memory markers. There was a trend towards higher expression of interleukin-2 from B*57-KF11 restricted CD8 T cells although this difference was not significant. Nevertheless both B*57 and B*35/53-restricted responses were relatively potent as reflected by the propensity of CD8 T cells to escape in p24 and Nef, respectively.
  
  
  CONCLUSIONS
  Differential protein targeting rather than the quality of T-cell responses appears to be a major distinguishing feature of HIV-specific CD8 T cells induced in B*57 carriers. These data suggest that viral fitness costs associated with CD8 T-cell pressure is an important factor determining differences in the viral load among HIV-infected patients.
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Alabama, USA.
authors.forename: Anju
authors.initials: A
authors.lastname: Bansal
authors.forename: Ling
authors.initials: L
authors.lastname: Yue
authors.forename: Joan
authors.initials: J
authors.lastname: Conway
authors.forename: Karina
authors.initials: K
authors.lastname: Yusim
authors.forename: Jianming
authors.initials: J
authors.lastname: Tang
authors.forename: John
authors.initials: J
authors.lastname: Kappes
authors.forename: Richard A
authors.initials: RA
authors.lastname: Kaslow
authors.forename: Craig M
authors.initials: CM
authors.lastname: Wilson
authors.forename: Paul A
authors.initials: PA
authors.lastname: Goepfert
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002908:Chronic Disease; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology; D020022:Genetic Predisposition to Disease; 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; D006680:HLA Antigens / Q000276:immunology*; D015235:HLA-B Antigens / Q000276:immunology; D015797:HLA-B35 Antigen / Q000276:immunology*; D006801:Humans; D016056:Immunodominant Epitopes / Q000235:genetics / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis; D008969:Molecular Sequence Data; D009154:Mutation; D011379:Prognosis; D019562:Viral Load; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology
chemical_list: D015683:Gene Products, gag; D016655:HIV Core Protein p24; D006680:HLA Antigens; D015235:HLA-B Antigens; D015797:HLA-B35 Antigen; C078438:HLA-B53 antigen; C103707:HLA-B57 antigen; D016056:Immunodominant Epitopes; D007376:Interleukin-2; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1; C514799:p24 protein, Human Immunodeficiency Virus Type 1