title: A nonprogressive clinical course in HIV-infected individuals expressing human leukocyte antigen B57/5801 is associated with preserved CD8+ T lymphocyte responsiveness to the HW9 epitope in Nef.
abstract: The human leukocyte antigen (HLA) B57 allele and the closely related HLA-B5801 allele are overrepresented among human immunodeficiency virus type 1 (HIV-1)-infected individuals with a long-term nonprogressive clinical course of disease (known as "long-term nonprogressors" [LTNPs]). These alleles are, however, also present among individuals with normal disease progression (known as "progressors"). In a comparison of HLA-B57/5801-expressing progressors and LTNPs, we observed a similar prevalence of escape mutations in 4 Nef epitopes and a similar reactivity of CD8+ T cells against 3 of 4 of these epitopes and their autologous escape variants. However, LTNPs tended to have frequent and preserved CD8+ T cell interferon-gamma responses against the wild-type HW9 Nef epitope, whereas progressors did not maintain a specific CD8+ T cell response. This finding is in line with the findings of a more exhausted phenotype of CD8+ T cells in progressors, as is demonstrated by their enhanced level of expression of inhibitory receptor "programmed death 1" (PD-1). The results of the present study suggest that preservation of HW9-specific T cell responses is associated with a more benign clinical course of infection.
authors.affiliation: Sanquin Research, Landsteiner Laboratory, and Center for Infectious Diseases and Immunity Amsterdam at the Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Marjon
authors.initials: M
authors.lastname: Navis
authors.forename: Ingrid M M
authors.initials: IM
authors.lastname: Schellens
authors.forename: Peter
authors.initials: P
authors.lastname: van Swieten
authors.forename: José A M
authors.initials: JA
authors.lastname: Borghans
authors.forename: Frank
authors.initials: F
authors.lastname: Miedema
authors.forename: Neeltje A
authors.initials: NA
authors.lastname: Kootstra
authors.forename: Debbie
authors.initials: D
authors.lastname: van Baarle
authors.forename: Hanneke
authors.initials: H
authors.lastname: Schuitemaker
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis / Q000276:immunology; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis / Q000276:immunology; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D015658:HIV Infections / Q000235:genetics / Q000276:immunology* / Q000821:virology; D020276:HIV Long-Term Survivors; D015497:HIV-1 / Q000276:immunology*; D015235:HLA-B Antigens / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D006801:Humans; D061026:Programmed Cell Death 1 Receptor; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D018984:Epitopes, T-Lymphocyte; D015235:HLA-B Antigens; C103707:HLA-B57 antigen; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1