The ER folding sensor UGGT1 acts on TAPBPR-chaperoned peptide-free MHC I
Adaptive immune responses are triggered by antigenic peptides presented on major histocompatibility complex class I (MHC I) at the surface of pathogen-infected or cancerous cells. Formation of stable peptide-MHC I complexes is facilitated by tapasin and TAPBPR, two related MHC I-specific chaperones...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2023-06-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/85432 |
| _version_ | 1797785719592189952 |
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| author | Lina Sagert Christian Winter Ina Ruppert Maximilian Zehetmaier Christoph Thomas Robert Tampé |
| author_facet | Lina Sagert Christian Winter Ina Ruppert Maximilian Zehetmaier Christoph Thomas Robert Tampé |
| author_sort | Lina Sagert |
| collection | DOAJ |
| description | Adaptive immune responses are triggered by antigenic peptides presented on major histocompatibility complex class I (MHC I) at the surface of pathogen-infected or cancerous cells. Formation of stable peptide-MHC I complexes is facilitated by tapasin and TAPBPR, two related MHC I-specific chaperones that catalyze selective loading of suitable peptides onto MHC I in a process called peptide editing or proofreading. On their journey to the cell surface, MHC I complexes must pass a quality control step performed by UGGT1, which senses the folding status of the transiting N-linked glycoproteins in the endoplasmic reticulum (ER). UGGT1 reglucosylates non-native glycoproteins and thereby allows them to revisit the ER folding machinery. Here, we describe a reconstituted in-vitro system of purified human proteins that enabled us to delineate the function of TAPBPR during the UGGT1-catalyzed quality control and reglucosylation of MHC I. By combining glycoengineering with liquid chromatography-mass spectrometry, we show that TAPBPR promotes reglucosylation of peptide-free MHC I by UGGT1. Thus, UGGT1 cooperates with TAPBPR in fulfilling a crucial function in the quality control mechanisms of antigen processing and presentation. |
| first_indexed | 2024-03-13T00:57:59Z |
| format | Article |
| id | doaj.art-4afe7db9f697492296b426c4fb3a9539 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-03-13T00:57:59Z |
| publishDate | 2023-06-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-4afe7db9f697492296b426c4fb3a95392023-07-06T14:40:09ZengeLife Sciences Publications LtdeLife2050-084X2023-06-011210.7554/eLife.85432The ER folding sensor UGGT1 acts on TAPBPR-chaperoned peptide-free MHC ILina Sagert0Christian Winter1Ina Ruppert2https://orcid.org/0000-0002-0448-2815Maximilian Zehetmaier3Christoph Thomas4https://orcid.org/0000-0001-7441-1089Robert Tampé5https://orcid.org/0000-0002-0403-2160Institute of Biochemistry, Biocenter, Goethe University Frankfurt, Frankfurt am Main, GermanyInstitute of Biochemistry, Biocenter, Goethe University Frankfurt, Frankfurt am Main, GermanyInstitute of Biochemistry, Biocenter, Goethe University Frankfurt, Frankfurt am Main, GermanyInstitute of Biochemistry, Biocenter, Goethe University Frankfurt, Frankfurt am Main, GermanyInstitute of Biochemistry, Biocenter, Goethe University Frankfurt, Frankfurt am Main, GermanyInstitute of Biochemistry, Biocenter, Goethe University Frankfurt, Frankfurt am Main, GermanyAdaptive immune responses are triggered by antigenic peptides presented on major histocompatibility complex class I (MHC I) at the surface of pathogen-infected or cancerous cells. Formation of stable peptide-MHC I complexes is facilitated by tapasin and TAPBPR, two related MHC I-specific chaperones that catalyze selective loading of suitable peptides onto MHC I in a process called peptide editing or proofreading. On their journey to the cell surface, MHC I complexes must pass a quality control step performed by UGGT1, which senses the folding status of the transiting N-linked glycoproteins in the endoplasmic reticulum (ER). UGGT1 reglucosylates non-native glycoproteins and thereby allows them to revisit the ER folding machinery. Here, we describe a reconstituted in-vitro system of purified human proteins that enabled us to delineate the function of TAPBPR during the UGGT1-catalyzed quality control and reglucosylation of MHC I. By combining glycoengineering with liquid chromatography-mass spectrometry, we show that TAPBPR promotes reglucosylation of peptide-free MHC I by UGGT1. Thus, UGGT1 cooperates with TAPBPR in fulfilling a crucial function in the quality control mechanisms of antigen processing and presentation.https://elifesciences.org/articles/85432antigen processingER quality controlMHC I chaperonesglycoproteinsadaptive immunitypeptide editing |
| spellingShingle | Lina Sagert Christian Winter Ina Ruppert Maximilian Zehetmaier Christoph Thomas Robert Tampé The ER folding sensor UGGT1 acts on TAPBPR-chaperoned peptide-free MHC I eLife antigen processing ER quality control MHC I chaperones glycoproteins adaptive immunity peptide editing |
| title | The ER folding sensor UGGT1 acts on TAPBPR-chaperoned peptide-free MHC I |
| title_full | The ER folding sensor UGGT1 acts on TAPBPR-chaperoned peptide-free MHC I |
| title_fullStr | The ER folding sensor UGGT1 acts on TAPBPR-chaperoned peptide-free MHC I |
| title_full_unstemmed | The ER folding sensor UGGT1 acts on TAPBPR-chaperoned peptide-free MHC I |
| title_short | The ER folding sensor UGGT1 acts on TAPBPR-chaperoned peptide-free MHC I |
| title_sort | er folding sensor uggt1 acts on tapbpr chaperoned peptide free mhc i |
| topic | antigen processing ER quality control MHC I chaperones glycoproteins adaptive immunity peptide editing |
| url | https://elifesciences.org/articles/85432 |
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