title: Identification of a conserved universal Th epitope in HIV-1 reverse transcriptase that is processed and presented to HIV-specific CD4+ T cells by at least four unrelated HLA-DR molecules.
abstract: CD4+ Th cells play an important role in the induction and maintenance of specific T cell immunity. Indications for a protective role of CD4+ T cells against HIV-1 infection were found in subjects who were able to control HIV-1 viremia as well as in highly HIV-1-exposed, yet seronegative, individuals. This study describes the identification of an HIV-1-specific Th epitope that exhibits high affinity binding as well as high immunogenicity in the context of at least four different HLA-DR molecules that together cover 50-60% of the Caucasian, Oriental, and Negroid populations. This HIV-1 reverse transcriptase-derived peptide (RT171-190) is highly conserved among different HIV-1 isolates. Importantly, stimulation of PBL cultures from HIV-1 seronegative donors with this peptide resulted in Thl-type lymphocytes capable of efficient recognition of HIV-1-pulsed APCs. Taken together, these data indicate that peptide RT171-190 constitutes an attractive component of vaccines aiming at induction or enhancement of HIV-1-specific T cell immunity.
authors.affiliation: Department of Immunohematology and Blood Bank, Leiden University Medical Center, The Netherlands. shvdburg@worldonline.nl
authors.forename: S H
authors.initials: SH
authors.lastname: van der Burg
authors.forename: K M
authors.initials: KM
authors.lastname: Kwappenberg
authors.forename: A
authors.initials: A
authors.lastname: Geluk
authors.forename: M
authors.initials: M
authors.lastname: van der Kruk
authors.forename: O
authors.initials: O
authors.lastname: Pontesilli
authors.forename: E
authors.initials: E
authors.lastname: Hovenkamp
authors.forename: K L
authors.initials: KL
authors.lastname: Franken
authors.forename: K E
authors.initials: KE
authors.lastname: van Meijgaarden
authors.forename: J W
authors.initials: JW
authors.lastname: Drijfhout
authors.forename: T H
authors.initials: TH
authors.lastname: Ottenhoff
authors.forename: C J
authors.initials: CJ
authors.lastname: Melief
authors.forename: R
authors.initials: R
authors.lastname: Offringa
mesh_terms: D000595:Amino Acid Sequence; D017951:Antigen Presentation; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology / Q000276:immunology / Q000821:virology; D002999:Clone Cells; D017124:Conserved Sequence; D016207:Cytokines / Q000096:biosynthesis; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D054303:HIV Reverse Transcriptase / Q000276:immunology* / Q000378:metabolism; D015497:HIV-1 / Q000276:immunology*; D006684:HLA-DR Antigens / Q000378:metabolism*; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000201:enzymology / Q000276:immunology* / Q000821:virology; D006377:T-Lymphocytes, Helper-Inducer / Q000201:enzymology / Q000276:immunology* / Q000821:virology
chemical_list: D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D006684:HLA-DR Antigens; D010455:Peptides; D054303:HIV Reverse Transcriptase