PMID- 9382849
OWN - NLM
STAT- MEDLINE
DCOM- 19980219
LR  - 20190728
IS  - 0960-9822 (Print)
IS  - 0960-9822 (Linking)
VI  - 7
IP  - 12
DP  - 1997 Dec 1
TI  - HLA-DO is a negative modulator of HLA-DM-mediated MHC class II peptide loading.
PG  - 950-7
AB  - BACKGROUND: Class II molecules of the major histocompatibility complex become 
      loaded with antigenic peptides after dissociation of invariant chainderived 
      peptides (CLIP) from the peptide-binding groove. The human leukocyte antigen 
      (HLA)-DM is a prerequisite for this process, which takes place in specialised 
      intracellular compartments. HLA-DM catalyses the peptide-exchange process, 
      simultaneously functioning as a peptide 'editor', favouring the presentation of 
      stably binding peptides. Recently, HLA-DO, an unconventional class II molecule, 
      has been found associated with HLA-DM in B cells, yet its function has remained 
      elusive. RESULTS: The function of the HLA-DO complex was investigated by 
      expression of both chains of the HLA-DO heterodimer (either alone or fused to 
      green fluorescent protein) in human Mel JuSo cells. Expression of HLA-DO resulted 
      in greatly enhanced surface expression of CLIP via HLA-DR3, the conversion of 
      class II complexes to the SDS-unstable phenotype and reduced antigen presentation 
      to T-cell clones. Analysis of peptides eluted from HLA-DR3 demonstrated that CLIP 
      was the major peptide bound to class II in the HLA-DO transfectants. Peptide 
      exchange assays in vitro revealed that HLA-DO functions directly at the level of 
      class II peptide loading by inhibiting the catalytic action of HLA-DM. 
      CONCLUSIONS: HLA-DO is a negative modulator of HLA-DM. By stably associating with 
      HLA-DM, the catalytic action of HLA-DM on class II peptide loading is inhibited. 
      HLA-DO thus affects the peptide repertoire that is eventually presented to the 
      immune system by MHC class II molecules.
FAU - van Ham, S M
AU  - van Ham SM
AD  - Department of Cellular Biochemistry, The Netherlands Cancer Institute, 
      Plesmanlaan 121, 1066, CX Amsterdam, The Netherlands. vanham@nki.nl
FAU - Tjin, E P
AU  - Tjin EP
FAU - Lillemeier, B F
AU  - Lillemeier BF
FAU - Gruneberg, U
AU  - Gruneberg U
FAU - van Meijgaarden, K E
AU  - van Meijgaarden KE
FAU - Pastoors, L
AU  - Pastoors L
FAU - Verwoerd, D
AU  - Verwoerd D
FAU - Tulp, A
AU  - Tulp A
FAU - Canas, B
AU  - Canas B
FAU - Rahman, D
AU  - Rahman D
FAU - Ottenhoff, T H
AU  - Ottenhoff TH
FAU - Pappin, D J
AU  - Pappin DJ
FAU - Trowsdale, J
AU  - Trowsdale J
FAU - Neefjes, J
AU  - Neefjes J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Curr Biol
JT  - Current biology : CB
JID - 9107782
RN  - 0 (Antigens, Differentiation, B-Lymphocyte)
RN  - 0 (H-2O antigen)
RN  - 0 (H2-M antigens)
RN  - 0 (HLA-D Antigens)
RN  - 0 (HLA-DM antigens)
RN  - 0 (HLA-DO antigens)
RN  - 0 (HLA-DR3 Antigen)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (invariant chain)
SB  - IM
MH  - Amino Acid Sequence
MH  - *Antigen Presentation
MH  - Antigens, Differentiation, B-Lymphocyte/metabolism
MH  - Cell Line
MH  - HLA-D Antigens/genetics/*metabolism
MH  - HLA-DR3 Antigen/metabolism
MH  - Histocompatibility Antigens Class II/*metabolism
MH  - Humans
MH  - Molecular Sequence Data
MH  - Recombinant Fusion Proteins/genetics/metabolism
MH  - Transfection
EDAT- 1998/02/21 00:00
MHDA- 1998/02/21 00:01
CRDT- 1998/02/21 00:00
PHST- 1998/02/21 00:00 [pubmed]
PHST- 1998/02/21 00:01 [medline]
PHST- 1998/02/21 00:00 [entrez]
AID - S0960-9822(06)00414-3 [pii]
AID - 10.1016/s0960-9822(06)00414-3 [doi]
PST - ppublish
SO  - Curr Biol. 1997 Dec 1;7(12):950-7. doi: 10.1016/s0960-9822(06)00414-3.