title: Immunoprevalence of the CD4+ T-cell response to HIV Tat and Vpr proteins is provided by clustered and disperse epitopes, respectively.
abstract: Recent studies have suggested including nonstructural proteins as Tat and Vpr in HIV vaccines. However, little is known about the CD4+ T-cell response that these small proteins induce in humans. We have therefore evaluated these responses by in vitro priming experiments of CD4+ T lymphocytes harvested in healthy donors. In the Tat protein, only one peptide primed CD4+ T cells of eight HLA unrelated healthy donors. T cells induced by this peptide recognized immature DC loaded with the native Tat protein and are restricted by multiple HLA-DR molecules, in agreement with its binding capacity. This peptide was therefore processed in an appropriate manner and was highly immunoprevalent. CD4+ T-cell response to Vpr peptides was more disperse and involved six different peptides depending on the HLA-DR molecules of the donors. Two overlapping peptides were T-cell stimulating in at least half of the donors. T-cell response to Vpr in multiple donors is the result of a combination of several CD4+ T-cell epitopes with good to moderate immunoprevalence. Altogether, our results show that the frequency of responders to HIV Tat or Vpr proteins relies on one or multiple CD4+ T-cell epitopes, respectively.
authors.affiliation: CEA, Institute of Biology and technologies (iBiTecS), SIMOPRO, Gif Sur Yvette, France.
authors.forename: Florence A
authors.initials: FA
authors.lastname: Castelli
authors.forename: Diane
authors.initials: D
authors.lastname: Houitte
authors.forename: Gaetan
authors.initials: G
authors.lastname: Munier
authors.forename: Natacha
authors.initials: N
authors.lastname: Szely
authors.forename: Alain
authors.initials: A
authors.lastname: Lecoq
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Briand
authors.forename: Sylviane
authors.initials: S
authors.lastname: Muller
authors.forename: Bernard
authors.initials: B
authors.lastname: Maillere
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015696:Gene Products, tat / Q000276:immunology*; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D054325:vpr Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte; D015696:Gene Products, tat; D006684:HLA-DR Antigens; D010446:Peptide Fragments; D054325:vpr Gene Products, Human Immunodeficiency Virus