Major histocompatibility complex class II-dependent unfolding, transport, and degradation of endogenous proteins
We have analyzed the ability of major histocompatibility (MHC) class II molecules to capture proteins in the biosynthetic pathway and whether this may be associated with MHC class II-dependent antigen processing. When coexpressed with HLA-DR 4 molecules in HeLa cells, influenza hemagglutinin was inhibited from folding and trimerization in the biosynthetic pathway, targeted to endosomal compartments, and rapidly degraded. Due to the interaction with MHC class II molecules, therefore, unfolded forms of hemagglutinin were bypassing the quality control mechanism of the secretory pathway. More important, however, the transport, endocytosis, and rapid degradation of unfolded hemagglutinin in the presence of MHC class II molecules suggest that proteins captured in the endoplasmic reticulum by class II molecules may become substrates for antigen processing and presentation to CD4-positive T cells. In insect cells we show that this phenomenon is not restricted to a few proteins such as hemagglutinin. A highly heterogeneous mixture of proteins from the endoplasmic reticulum including coexpressed hemagglutinin can form stable complexes with soluble HLA-DR alpha and beta chains that were transported into the supernatant. This mechanism may gain biological significance in abnormal situations associated with accumulation of unfolded or malfolded proteins in the endoplasmic reticulum, for example during viral infections.
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
1997 |
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| Erschienen: |
1997 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:272 |
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| Enthalten in: |
The Journal of biological chemistry - 272(1997), 46 vom: 14. Nov., Seite 29127-36 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Aichinger, G [VerfasserIn] |
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| Themen: |
HLA-DR4 Antigen |
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| Anmerkungen: |
Date Completed 11.12.1997 Date Revised 09.02.2021 published: Print Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM093050321 |
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| 100 | 1 | |a Aichinger, G |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Major histocompatibility complex class II-dependent unfolding, transport, and degradation of endogenous proteins |
| 264 | 1 | |c 1997 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
| 338 | |a Band |b nc |2 rdacarrier | ||
| 500 | |a Date Completed 11.12.1997 | ||
| 500 | |a Date Revised 09.02.2021 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a We have analyzed the ability of major histocompatibility (MHC) class II molecules to capture proteins in the biosynthetic pathway and whether this may be associated with MHC class II-dependent antigen processing. When coexpressed with HLA-DR 4 molecules in HeLa cells, influenza hemagglutinin was inhibited from folding and trimerization in the biosynthetic pathway, targeted to endosomal compartments, and rapidly degraded. Due to the interaction with MHC class II molecules, therefore, unfolded forms of hemagglutinin were bypassing the quality control mechanism of the secretory pathway. More important, however, the transport, endocytosis, and rapid degradation of unfolded hemagglutinin in the presence of MHC class II molecules suggest that proteins captured in the endoplasmic reticulum by class II molecules may become substrates for antigen processing and presentation to CD4-positive T cells. In insect cells we show that this phenomenon is not restricted to a few proteins such as hemagglutinin. A highly heterogeneous mixture of proteins from the endoplasmic reticulum including coexpressed hemagglutinin can form stable complexes with soluble HLA-DR alpha and beta chains that were transported into the supernatant. This mechanism may gain biological significance in abnormal situations associated with accumulation of unfolded or malfolded proteins in the endoplasmic reticulum, for example during viral infections | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a HLA-DR4 Antigen |2 NLM | |
| 650 | 7 | |a Hemagglutinin Glycoproteins, Influenza Virus |2 NLM | |
| 650 | 7 | |a Immunodominant Epitopes |2 NLM | |
| 650 | 7 | |a Proteins |2 NLM | |
| 650 | 7 | |a Recombinant Proteins |2 NLM | |
| 700 | 1 | |a Karlsson, L |e verfasserin |4 aut | |
| 700 | 1 | |a Jackson, M R |e verfasserin |4 aut | |
| 700 | 1 | |a Vestberg, M |e verfasserin |4 aut | |
| 700 | 1 | |a Vaughan, J H |e verfasserin |4 aut | |
| 700 | 1 | |a Teyton, L |e verfasserin |4 aut | |
| 700 | 1 | |a Lechler, R I |e verfasserin |4 aut | |
| 700 | 1 | |a Peterson, P A |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t The Journal of biological chemistry |d 1945 |g 272(1997), 46 vom: 14. Nov., Seite 29127-36 |w (DE-627)NLM000004995 |x 1083-351X |7 nnns |
| 773 | 1 | 8 | |g volume:272 |g year:1997 |g number:46 |g day:14 |g month:11 |g pages:29127-36 |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 272 |j 1997 |e 46 |b 14 |c 11 |h 29127-36 | ||