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Transport and intracellular distribution of MHC class II molecules and associated invariant chain in normal and antigen-processing mutant cell lines.
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MedLine Citation:
PMID:  8207055     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We have compared the intracellular transport and subcellular distribution of MHC class II-invariant chain complexes in a wild-type HLA-DR3 homozygous cell line and a mutant cell line, T2.DR3. The latter has a defect in antigen processing and accumulates HLA-DR3 molecules associated with an invariant chain-derived peptide (CLIP) rather than the normal complement of peptides derived from endocytosed proteins. We find that in the wild-type cells, CLIP is transiently associated with HLA-DR3 molecules, suggesting that the peptide is a normal class II-associated intermediate generated during proteolysis of the invariant chain. In the mutant cell line proteolysis of the invariant chain is less efficient, and HLA-DR3/CLIP complexes are generated much more slowly. Examination of the mutant cell line by immunoelectronmicroscopy shows that class II-invariant chain complexes accumulate intracellularly in large acidic vesicles which contain lysosomal markers, including beta-hexosaminidase, cathepsin D, and the lysosomal membrane protein CD63. The markers in these vesicles are identical to those seen in the class II-containing vesicles (MIICs) seen in the wild-type cells but the morphology is drastically different. The vesicles in the mutant cells are endocytic, as measured by the internalization of BSA-gold conjugates. The implication of these findings for antigen processing in general and the nature of the mutation in particular are discussed.
Authors:
J M Riberdy; R R Avva; H J Geuze; P Cresswell
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of cell biology     Volume:  125     ISSN:  0021-9525     ISO Abbreviation:  J. Cell Biol.     Publication Date:  1994 Jun 
Date Detail:
Created Date:  1994-07-12     Completed Date:  1994-07-12     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0375356     Medline TA:  J Cell Biol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1225-37     Citation Subset:  IM    
Affiliation:
Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06510.
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MeSH Terms
Descriptor/Qualifier:
Antigen Presentation / genetics*
Antigens, Differentiation, B-Lymphocyte*
B-Lymphocytes / immunology*,  ultrastructure
Biological Markers
Biological Transport
Cell Line
Endocytosis
Frozen Sections
HLA-DR3 Antigen / genetics,  isolation & purification,  metabolism
Histocompatibility Antigens Class II / genetics,  isolation & purification,  metabolism*
Homozygote
Humans
Immunohistochemistry
Microscopy, Immunoelectron
Mutation
Peptide Fragments / isolation & purification,  metabolism*
Grant Support
ID/Acronym/Agency:
AI23081/AI/NIAID NIH HHS; NWO PG 900-523-094/PG/OAPP OPHS HHS
Chemical
Reg. No./Substance:
0/Antigens, Differentiation, B-Lymphocyte; 0/Biological Markers; 0/HLA-DR3 Antigen; 0/Histocompatibility Antigens Class II; 0/Peptide Fragments; 0/invariant chain
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Full Text
Journal Information
Journal ID (nlm-ta): J Cell Biol
Journal ID (publisher-id): J. Cell Biol.
ISSN: 0021-9525
ISSN: 1540-8140
Publisher: The Rockefeller University Press
Article Information
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Print publication date: Day: 2 Month: 6 Year: 1994
Volume: 125 Issue: 6
First Page: 1225 Last Page: 1237
ID: 2290929
Publisher Id: 94266956
PubMed Id: 8207055

Transport and intracellular distribution of MHC class II molecules and associated invariant chain in normal and antigen-processing mutant cell lines


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