title: Natural mucosal antibodies reactive with first extracellular loop of CCR5 inhibit HIV-1 transport across human epithelial cells.
abstract: OBJECTIVE
  The genital mucosa represents the major site for initial host-HIV-1 contact. HIV-1-protective mucosal immunity has been identified either in subjects who despite repeated sexual exposure, remain seronegative (ESN) or in long-term non-progressor HIV-1-seropositive individuals (LTNP). As a subset of ESN and LTNP produce anti-CCR5 antibodies both at systemic and mucosal level, we studied the role of anti-CCR5 antibodies in blocking HIV transfer through human epithelial cells.
  
  
  METHODS
  To evaluate HIV-1-inhibitory activity by anti-CCR5 antibodies, a two-chambers system was established to model HIV-1 infection across the human mucosal epithelium. Moreover, peripheral blood mononuclear cells (PBMC) and a CCR5 transfected cell line were also used in a classical HIV-infectivity assay. CCR5-specific IgG and IgA were used to inhibit HIV replication.
  
  
  RESULTS
  Either serum or mucosal IgA to CCR5 were able to specifically block transcytosis of CCR5- but not CXCR4-HIV strains across a tight epithelial cell layer by interacting with the first extracellular loop of the receptor (amino acids YAAAQWDFGNTMCQ). Monoclonal antibodies against other regions of CCR5 had no effect on HIV transcytosis. Moreover, mucosal CCR5-specific IgA neutralized CCR5-tropic strains and SOS-JRFL pseudovirus replication in PBMC and CCR5 transfected cell lines respectively, with a mechanism different than that observed for transcytosis.
  
  
  CONCLUSIONS
  Anti-CCR5 Abs shed light on the immunological mechanisms involved in the control of HIV-1 infection in a model that can be considered an experimentum naturae for resistance to HIV. They could be useful in the design of new strategies against HIV infection at mucosal sites.
authors.affiliation: Institut Cochin, INSERM, CNRS, Paris, France.
authors.forename: Morgane
authors.initials: M
authors.lastname: Bomsel
authors.forename: Claudia
authors.initials: C
authors.lastname: Pastori
authors.forename: Daniela
authors.initials: D
authors.lastname: Tudor
authors.forename: Chiara
authors.initials: C
authors.lastname: Alberti
authors.forename: Severine
authors.initials: S
authors.lastname: Garcia
authors.forename: Davide
authors.initials: D
authors.lastname: Ferrari
authors.forename: Adriano
authors.initials: A
authors.lastname: Lazzarin
authors.forename: Lucia
authors.initials: L
authors.lastname: Lopalco
mesh_terms: D000328:Adult; D000906:Antibodies / Q000276:immunology*; D001681:Biological Assay; D001692:Biological Transport; D003106:Colon; D004847:Epithelial Cells / Q000276:immunology* / Q000821:virology; D000939:Epitopes; D005260:Female; D015658:HIV Infections / Q000276:immunology*; D018023:HIV Seronegativity / Q000276:immunology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology* / Q000821:virology; D008297:Male; D011485:Protein Binding; D019713:Receptors, CCR5 / Q000378:metabolism*; D012007:Rectum
chemical_list: D000906:Antibodies; D000939:Epitopes; D007070:Immunoglobulin A; D019713:Receptors, CCR5