PMID- 25637027
OWN - NLM
STAT- MEDLINE
DCOM- 20150424
LR  - 20220129
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Linking)
VI  - 194
IP  - 5
DP  - 2015 Mar 1
TI  - MHC class II presentation is controlled by the lysosomal small GTPase, Arl8b.
PG  - 2079-88
LID - 10.4049/jimmunol.1401072 [doi]
AB  - Dendritic cells (DCs) are specialized APCs with the ability to prime naive T 
      cells. DCs first sample Ags from the environment and then orchestrate their 
      processing and loading onto MHC class II (MHC II) Ag-presenting molecules in 
      lysosomes. Once MHC II molecules have bound a peptide, the MHC II-peptide complex 
      is delivered to the cell surface for presentation to CD4(+) T cells. Regulation 
      of Ag uptake via macropinocytosis and phagocytosis has been extensively studied, 
      as well as trafficking in early endocytic vesicles notably regulated by the small 
      GTPase Rab5 and its effectors. However, little is known about the regulators of 
      Ag delivery from early endosomes to lysosomal compartments where the proper pH, 
      proteases, MHC II, invariant chain, and HLA-DM reside, awaiting exogenous Ags for 
      loading. In this article, we report the crucial role of the small GTPase 
      ADP-ribosylation factor-like 8b (Arl8b) in MHC II presentation in DCs. We show 
      for the first time, to our knowledge, that Arl8b localizes to MHC II compartments 
      in DCs and regulates formation of MHC II-peptide complexes. Arl8b-silenced DCs 
      display a defect in MHC II-Ag complex formation and its delivery to the cell 
      surface during infection resulting in a defect in T cell recognition. Our results 
      highlight the role of Arl8b as a trafficking regulator of the late stage of 
      complex formation and MHC II presentation in DCs.
CI  - Copyright (c) 2015 by The American Association of Immunologists, Inc.
FAU - Michelet, Xavier
AU  - Michelet X
AD  - Division of Rheumatology, Immunology and Allergy, Department of Medicine, Brigham 
      and Women's Hospital, Harvard Medical School, Boston, MA 02115;
FAU - Garg, Salil
AU  - Garg S
AD  - Division of Rheumatology, Immunology and Allergy, Department of Medicine, Brigham 
      and Women's Hospital, Harvard Medical School, Boston, MA 02115;
FAU - Wolf, Benjamin J
AU  - Wolf BJ
AD  - Division of Rheumatology, Immunology and Allergy, Department of Medicine, Brigham 
      and Women's Hospital, Harvard Medical School, Boston, MA 02115;
FAU - Tuli, Amit
AU  - Tuli A
AD  - Division of Rheumatology, Immunology and Allergy, Department of Medicine, Brigham 
      and Women's Hospital, Harvard Medical School, Boston, MA 02115; Division of Cell 
      Biology and Immunology, Institute of Microbial Technology, Chandigarh 160036, 
      India; and.
FAU - Ricciardi-Castagnoli, Paola
AU  - Ricciardi-Castagnoli P
AD  - Singapore Immunology Network, Agency for Science, Technology and Research, 138648 
      Singapore.
FAU - Brenner, Michael B
AU  - Brenner MB
AD  - Division of Rheumatology, Immunology and Allergy, Department of Medicine, Brigham 
      and Women's Hospital, Harvard Medical School, Boston, MA 02115; 
      mbrenner@research.bwh.harvard.edu.
LA  - eng
GR  - IA/I/14/2/501543/WTDBT_/DBT-Wellcome Trust India Alliance/India
GR  - 2R01 AI028973/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 - 20150130
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Antigens)
RN  - 0 (Arl8B protein, mouse)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (RNA, Small Interfering)
RN  - 9006-59-1 (Ovalbumin)
RN  - EC 3.6.5.2 (ADP-Ribosylation Factors)
SB  - IM
MH  - ADP-Ribosylation Factors/antagonists & inhibitors/genetics/*immunology
MH  - Animals
MH  - *Antigen Presentation
MH  - Antigens/immunology
MH  - Bone Marrow Cells/cytology/immunology
MH  - CD4-Positive T-Lymphocytes/cytology/*immunology
MH  - Cell Line
MH  - Chickens
MH  - Dendritic Cells/cytology/*immunology
MH  - Endosomes/immunology
MH  - Gene Expression Regulation
MH  - Histocompatibility Antigens Class II/genetics/*immunology
MH  - Lysosomes/*immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Ovalbumin/immunology
MH  - Primary Cell Culture
MH  - Protein Transport
MH  - RNA, Small Interfering/genetics/metabolism
MH  - Signal Transduction
MH  - Spleen/cytology/immunology
EDAT- 2015/02/01 06:00
MHDA- 2015/04/25 06:00
CRDT- 2015/02/01 06:00
PHST- 2015/02/01 06:00 [entrez]
PHST- 2015/02/01 06:00 [pubmed]
PHST- 2015/04/25 06:00 [medline]
AID - jimmunol.1401072 [pii]
AID - 10.4049/jimmunol.1401072 [doi]
PST - ppublish
SO  - J Immunol. 2015 Mar 1;194(5):2079-88. doi: 10.4049/jimmunol.1401072. Epub 2015 
      Jan 30.