Abstract
MHC class I molecules expressed in a calreticulin-deficient cell line (K42) assembled with beta 2-microglobulin (beta2-m) normally, but their subsequent loading with optimal peptides was defective. Suboptimally loaded class I molecules were released into the secretory pathway. This occurred despite the ability of newly synthesized class I to interact with the transporter associated with antigen processing (TAP) loading complex. The efficiency of peptide loading was reduced by 50%-80%, and impaired T cell recognition was observed for three out of four antigens tested. The peptide-loading function was specific to calreticulin, since the defect in K42 could be rectified by transfection with calreticulin but not a soluble form of calnexin, which shares its lectin-like activity.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigen Presentation*
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Antiporters / chemistry
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Biological Transport
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Calcium-Binding Proteins / physiology*
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Calreticulin
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Cells, Cultured
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Endoplasmic Reticulum / metabolism
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Heat-Shock Proteins / chemistry
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Histocompatibility Antigens Class I / analysis
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Histocompatibility Antigens Class I / chemistry*
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Histocompatibility Antigens Class I / physiology
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Immunoglobulins / chemistry
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Isomerases / chemistry
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Membrane Transport Proteins
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Mice
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Protein Disulfide-Isomerases
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Ribonucleoproteins / physiology*
Substances
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Antiporters
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Calcium-Binding Proteins
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Calreticulin
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Heat-Shock Proteins
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Histocompatibility Antigens Class I
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Immunoglobulins
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Membrane Transport Proteins
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Ribonucleoproteins
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tapasin
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Isomerases
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Pdia3 protein, mouse
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Protein Disulfide-Isomerases