HLA-DR molecules from an antigen-processing mutant cell line are associated with invariant chain peptides

THE invariant chain, which associates with the major histocompatibility complex (MHC) class II molecules in the endoplasmic reticulum, serves two functions important in antigen processing. First, it prevents class II molecules from binding peptides in the early stages of intracellular transport1-3....

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Bibliographic Details
Published in:Nature (London) 1992-12, Vol.360 (6403), p.474-477
Main Authors: Riberdy, Janice M, Newcomb, John R, Surman, Michael J, Barbosat, James A, Cresswell, Peter
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Antibodies, Monoclonal
Antigens
Biological and medical sciences
Cell Line
Cellular biology
Chromatography, High Pressure Liquid
Electrophoresis, Polyacrylamide Gel
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Histocompatibility antigens (hla, h-2 and other systems)
HLA-DR2 Antigen - chemistry
HLA-DR2 Antigen - genetics
HLA-DR2 Antigen - isolation & purification
Homozygote
Humans
Immunity (Disease)
Macromolecular Substances
Molecular immunology
Molecular Sequence Data
Molecules
Multidisciplinary Sciences
Mutation
Peptide Fragments - isolation & purification
Science & Technology
Science & Technology - Other Topics
Transfection
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Summary:THE invariant chain, which associates with the major histocompatibility complex (MHC) class II molecules in the endoplasmic reticulum, serves two functions important in antigen processing. First, it prevents class II molecules from binding peptides in the early stages of intracellular transport1-3. Second, it contains a cytoplasmic signal that targets the class II-invariant chain complex to an acidic endosomal compartment4-6. Proteolytic cleavage and subsequent dissociation of the invariant chain then occurs7,8, allowing peptides derived from endocytosed proteins to bind to released class II molecules before their expression at the cell surface3. Certain human cell lines that are mutant in one or more MHC-linked genes are defective in class II-restricted antigen processing9-11. Here we show that in transfectants of one of these cell lines, T2, this deficiency results in the association of a large proportion of class II molecules with a nested set of invariant-chain-derived peptides (class II-associated invariant chain peptides, or CLIP). HLA-DR3 molecules isolated from T2 transfectants can be efficiently loaded with antigenic peptides by exposure to a low pH in vitro, perhaps reflecting the in vivo conditions in which peptides associate with class II molecules12-14. Addition of synthetic CLIP inhibits the loading process, indicating that CLIP may define the region of the invariant chain responsible for obstructing the class II binding site.
ISSN:0028-0836
1476-4687
DOI:10.1038/360474a0