title: Cell type-specific proteasomal processing of HIV-1 Gag-p24 results in an altered epitope repertoire.
abstract: Proteasomes are critical for the processing of antigens for presentation through the major histocompatibility complex (MHC) class I pathway. HIV-1 Gag protein is a component of several experimental HIV-1 vaccines. Therefore, understanding the processing of HIV-1 Gag protein and the resulting epitope repertoire is essential. Purified proteasomes from mature dendritic cells (DC) and activated CD4(+) T cells from the same volunteer were used to cleave full-length Gag-p24 protein, and the resulting peptide fragments were identified by mass spectrometry. Distinct proteasomal degradation patterns and peptide fragments were unique to either mature DC or activated CD4(+) T cells. Almost half of the peptides generated were cell type specific. Two additional differences were observed in the peptides identified from the two cell types. These were in the HLA-B35-Px epitope and the HLA-B27-KK10 epitope. These epitopes have been linked to HIV-1 disease progression. Our results suggest that the source of generation of precursor MHC class I epitopes may be a critical factor for the induction of relevant epitope-specific cytotoxic T cells.
authors.affiliation: Henry Jackson Foundation for the Advancement of Military Medicine, 1600 East Gude Drive, Rockville, Maryland 20850, USA.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Steers
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Currier
authors.forename: Gustavo H
authors.initials: GH
authors.lastname: Kijak
authors.forename: Robert C
authors.initials: RC
authors.lastname: di Targiani
authors.forename: Ashima
authors.initials: A
authors.lastname: Saxena
authors.forename: Mary A
authors.initials: MA
authors.lastname: Marovich
authors.forename: Jerome H
authors.initials: JH
authors.lastname: Kim
authors.forename: Nelson L
authors.initials: NL
authors.lastname: Michael
authors.forename: Carl R
authors.initials: CR
authors.lastname: Alving
authors.forename: Mangala
authors.initials: M
authors.lastname: Rao
mesh_terms: D000595:Amino Acid Sequence; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology* / Q000276:immunology; D003713:Dendritic Cells / Q000201:enzymology* / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry* / Q000276:immunology*; D016655:HIV Core Protein p24 / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D015497:HIV-1 / Q000276:immunology; D015796:HLA-B27 Antigen / Q000276:immunology; D015797:HLA-B35 Antigen / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*
chemical_list: D018984:Epitopes, T-Lymphocyte; D016655:HIV Core Protein p24; D015796:HLA-B27 Antigen; D015797:HLA-B35 Antigen; D010446:Peptide Fragments; C514799:p24 protein, Human Immunodeficiency Virus Type 1; D046988:Proteasome Endopeptidase Complex