PMID- 25230751 OWN - NLM STAT- MEDLINE DCOM- 20150303 LR - 20211021 IS - 1550-6606 (Electronic) IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 193 IP - 9 DP - 2014 Nov 1 TI - Different antigen-processing activities in dendritic cells, macrophages, and monocytes lead to uneven production of HIV epitopes and affect CTL recognition. PG - 4322-4334 LID - 10.4049/jimmunol.1400491 [doi] AB - Dendritic cells (DCs), macrophages (MPs), and monocytes are permissive to HIV. Whether they similarly process and present HIV epitopes to HIV-specific CD8 T cells is unknown despite the critical role of peptide processing and presentation for recognition and clearance of infected cells. Cytosolic peptidases degrade endogenous proteins originating from self or pathogens, exogenous Ags preprocessed in endolysosomes, thus shaping the peptidome available for endoplasmic reticulum translocation, trimming, and MHC-I presentation. In this study, we compared the capacity of DCs, MPs, and monocyte cytosolic extracts to produce epitope precursors and epitopes. We showed differences in the proteolytic activities and expression levels of cytosolic proteases between monocyte-derived DCs and MPs and upon maturation with LPS, R848, and CL097, with mature MPs having the highest activities. Using cytosol as a source of proteases to degrade epitope-containing HIV peptides, we showed by mass spectrometry that the degradation patterns of long peptides and the kinetics and amount of antigenic peptides produced differed among DCs, MPs, and monocytes. Additionally, variable intracellular stability of HIV peptides prior to loading onto MHC may accentuate the differences in epitope availability for presentation by MHC-I between these subsets. Differences in peptide degradation led to 2- to 25-fold differences in the CTL responses elicited by the degradation peptides generated in DCs, MPs, and monocytes. Differences in Ag-processing activities between these subsets might lead to variations in the timing and efficiency of recognition of HIV-infected cells by CTLs and contribute to the unequal capacity of HIV-specific CTLs to control viral load. CI - Copyright (c) 2014 by The American Association of Immunologists, Inc. FAU - Dinter, Jens AU - Dinter J AD - Ragon Institute of MGH, MIT and Harvard, Massachusetts General Hospital, Harvard Medical School, Cambridge, MA, USA. FAU - Gourdain, Pauline AU - Gourdain P AD - Ragon Institute of MGH, MIT and Harvard, Massachusetts General Hospital, Harvard Medical School, Cambridge, MA, USA. FAU - Lai, Nicole Y AU - Lai NY AD - Ragon Institute of MGH, MIT and Harvard, Massachusetts General Hospital, Harvard Medical School, Cambridge, MA, USA. FAU - Duong, Ellen AU - Duong E AD - Ragon Institute of MGH, MIT and Harvard, Massachusetts General Hospital, Harvard Medical School, Cambridge, MA, USA. FAU - Bracho-Sanchez, Edith AU - Bracho-Sanchez E AD - Ragon Institute of MGH, MIT and Harvard, Massachusetts General Hospital, Harvard Medical School, Cambridge, MA, USA. FAU - Rucevic, Marijana AU - Rucevic M AD - Ragon Institute of MGH, MIT and Harvard, Massachusetts General Hospital, Harvard Medical School, Cambridge, MA, USA. FAU - Liebesny, Paul H AU - Liebesny PH AD - Ragon Institute of MGH, MIT and Harvard, Massachusetts General Hospital, Harvard Medical School, Cambridge, MA, USA. FAU - Xu, Yang AU - Xu Y AD - Ragon Institute of MGH, MIT and Harvard, Massachusetts General Hospital, Harvard Medical School, Cambridge, MA, USA. FAU - Shimada, Mariko AU - Shimada M AD - Ragon Institute of MGH, MIT and Harvard, Massachusetts General Hospital, Harvard Medical School, Cambridge, MA, USA. FAU - Ghebremichael, Musie AU - Ghebremichael M AD - Ragon Institute of MGH, MIT and Harvard, Massachusetts General Hospital, Harvard Medical School, Cambridge, MA, USA. FAU - Kavanagh, Daniel G AU - Kavanagh DG AD - Ragon Institute of MGH, MIT and Harvard, Massachusetts General Hospital, Harvard Medical School, Cambridge, MA, USA. FAU - Le Gall, Sylvie AU - Le Gall S AD - Ragon Institute of MGH, MIT and Harvard, Massachusetts General Hospital, Harvard Medical School, Cambridge, MA, USA. LA - eng GR - R01 AI084106/AI/NIAID NIH HHS/United States GR - R01 AI084753/AI/NIAID NIH HHS/United States GR - AI084106/AI/NIAID NIH HHS/United States GR - AI084753/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20140917 PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Antigens, Surface) RN - 0 (Epitopes) RN - 0 (Peptides) RN - 0 (Toll-Like Receptors) RN - EC 3.4.- (Peptide Hydrolases) RN - EC 3.4.25.1 (Proteasome Endopeptidase Complex) SB - IM MH - Amino Acid Sequence MH - Animals MH - Antigen Presentation/*immunology MH - Antigens, Surface/metabolism MH - Cell Line, Transformed MH - Cytosol/immunology/metabolism MH - Dendritic Cells/*immunology/metabolism MH - Epitopes/*immunology MH - HIV/*immunology MH - HIV Infections/*immunology MH - Humans MH - Immunophenotyping MH - Leukocytes, Mononuclear/immunology/metabolism MH - Macrophages/*immunology/metabolism MH - Monocytes/*immunology/metabolism MH - Peptide Hydrolases/metabolism MH - Peptides/chemistry/immunology MH - Proteasome Endopeptidase Complex/metabolism MH - Protein Stability MH - Proteolysis MH - T-Lymphocytes, Cytotoxic/*immunology/metabolism MH - Toll-Like Receptors/metabolism PMC - PMC4201977 MID - NIHMS623662 EDAT- 2014/09/19 06:00 MHDA- 2015/03/04 06:00 PMCR- 2015/11/01 CRDT- 2014/09/19 06:00 PHST- 2014/09/19 06:00 [entrez] PHST- 2014/09/19 06:00 [pubmed] PHST- 2015/03/04 06:00 [medline] PHST- 2015/11/01 00:00 [pmc-release] AID - 10.4049/jimmunol.1400491 [doi] PST - ppublish SO - J Immunol. 2014 Nov 1;193(9):4322-4334. doi: 10.4049/jimmunol.1400491. Epub 2014 Sep 17.