PMID- 10480952
OWN - NLM
STAT- MEDLINE
DCOM- 19991013
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 38
DP  - 1999 Sep 17
TI  - Direct transport of newly synthesized HLA-DR from the trans-Golgi network to
      major histocompatibility complex class II containing compartments (MIICS)
      demonstrated using a novel tyrosine-sulfated chimera.
PG  - 27315-22
AB  - Binding of antigenic peptides to major histocompatibility complex (MHC) class II 
      glycoproteins occurs in specialized endocytic compartments of antigen-presenting 
      cells, which in man are termed MIICs. Newly synthesized MHC class II molecules
      are transported from the trans-Golgi network to MIICs, but previous studies of
      this important step in antigen processing have failed to conclusively determine
      whether most immature MHC class II complexes are transported directly to the
      processing compartments or are first transiently exposed at the cell surface. To 
      attempt to resolve this question, I constructed a chimeric HLA-DRalpha chain
      containing two optimal tyrosine sulfation motifs. When expressed in a human B
      lymphoblastoid cell line lacking functional DRalpha chains, the chimera was
      correctly incorporated into complexes containing endogenous beta and invariant
      chains, transported to the trans-Golgi network, and efficiently sulfated.
      Pulse-chase experiments showed that the sulfated complexes were rapidly
      transported to processing compartments with kinetics consistent with direct
      transport from the trans-Golgi network. The rate of maturation was not
      significantly altered in cells expressing a temperature-sensitive mutant of
      dynamin under conditions where the endocytosis of transferrin was inhibited by
      95%, confirming that endocytosis was not required for delivery to MIICs.
      Maturation of MHC class II-containing complexes was inhibited by aluminum
      fluoride and brefeldin A, indicating the involvement of heterotrimeric G-proteins
      and ADP-ribosylation factor in the transport event(s). The procedure described
      provides a unique mechanism to study critical events in antigen processing and
      presentation.
FAU - Davidson, H W
AU  - Davidson HW
AD  - Department of Clinical Biochemistry, Cambridge Institute for Medical Research,
      University of Cambridge, Wellcome Trust/MRC Building, Cambridge CB2 2XY, United
      Kingdom. hd162@cam.ac.uk
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (HLA-DR Antigens)
RN  - 0 (HLA-DR alpha-Chains)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Sulfates)
RN  - 0 (Transferrin)
RN  - 42HK56048U (Tyrosine)
RN  - EC 3.6.1.- (GTP Phosphohydrolases)
RN  - EC 3.6.5.5 (Dynamins)
SB  - IM
MH  - Amino Acid Sequence
MH  - Biological Transport, Active
MH  - Dynamins
MH  - Endocytosis
MH  - GTP Phosphohydrolases/metabolism
MH  - Golgi Apparatus/*metabolism
MH  - HLA-DR Antigens/*metabolism
MH  - HLA-DR alpha-Chains
MH  - Histocompatibility Antigens Class II/*metabolism
MH  - Humans
MH  - Male
MH  - Molecular Sequence Data
MH  - Recombinant Fusion Proteins/*metabolism
MH  - Sulfates/metabolism
MH  - Transferrin
MH  - Tumor Cells, Cultured
MH  - Tyrosine
EDAT- 1999/09/10 00:00
MHDA- 1999/09/10 00:01
CRDT- 1999/09/10 00:00
PHST- 1999/09/10 00:00 [pubmed]
PHST- 1999/09/10 00:01 [medline]
PHST- 1999/09/10 00:00 [entrez]
AID - 10.1074/jbc.274.38.27315 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Sep 17;274(38):27315-22. doi: 10.1074/jbc.274.38.27315.