HLA-DR associates with specific stress proteins and is retained in the endoplasmic reticulum in invariant chain negative cells
| Autor: | Benjamin D. Schwartz, Michael Green, K A Hruska, D W McCourt, W T Schaiff |
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| Rok vydání: | 1992 |
| Předmět: |
Molecular Sequence Data
Immunology Peptide binding Biology Endoplasmic Reticulum Transfection 3T3 cells Turn (biochemistry) Mice Western blot HLA-DR Fluorescence microscope medicine Animals Humans Immunology and Allergy HSP70 Heat-Shock Proteins Amino Acid Sequence Heat-Shock Proteins Membrane Glycoproteins medicine.diagnostic_test Endoplasmic reticulum Membrane Proteins 3T3 Cells HLA-DR Antigens Articles Precipitin Tests Molecular biology Molecular Weight medicine.anatomical_structure Microscopy Fluorescence |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| DOI: | 10.1084/jem.176.3.657 |
| Popis: | The major histocompatibility complex class II molecules are composed of two polymorphic chains which, in cells normally expressing them, transiently associate with a third, nonpolymorphic molecule, the invariant chain (Ii). To determine differences in the biology of class II molecules synthesized in the presence or absence of Ii, a comparative study was performed of BALB/c 3T3 cells that had been transfected with human class II HLA-DR molecules with or without cotransfection with human Ii. It was observed that in the absence of Ii, at least three high molecular weight proteins coimmunoprecipitate with HLA-DR molecules. These proteins did not coimmunoprecipitate with HLA-DR from cells cotransfected with Ii, nor did they coimmunoprecipitate with class I molecules from any of the transfectants. NH2-terminal sequence and/or Western blot analysis revealed the identity of two of the proteins as the endoplasmic reticulum (ER) resident stress proteins GRP94 and ERp72. Neither of these proteins was found to have an increased level of synthesis in the Ii- versus the Ii+ transfectants, indicating that their synthesis was not induced over constitutive levels. Fluorescence microscopy revealed that in the Ii- transfectants, the majority of the HLA-DR molecules were present in the ER, whereas in the Ii+ transfectants, the HLA-DR molecules were found in vesicular structures. We hypothesize that in the absence of Ii, ER resident stress proteins bind to class II molecules and retain them in the ER. This process, in turn, could prevent class II molecules from exiting the ER with endogenous peptides bound in their peptide binding cleft, and therefore could minimize autoimmune responses to endogenously processed self-peptides. |
| Databáze: | OpenAIRE |
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