The Small GTPase Rab7 Regulates Antigen Processing in B Cells in a Possible Interplay with Autophagy Machinery

In B cells, antigen processing and peptide-antigen (pAg) presentation is essential to ignite high-affinity antibody responses with the help of cognate T cells. B cells efficiently internalize and direct specific antigens for processing and loading onto MHCII. This critical step, which enables pAg pr...

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Autores principales: Runsala, Marika, Kuokkanen, Elina, Uski, Eveliina, Šuštar, Vid, Balci, Meryem Özge, Rajala, Johanna, Paavola, Vilma, Mattila, Pieta K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10649364/
https://www.ncbi.nlm.nih.gov/pubmed/37947644
http://dx.doi.org/10.3390/cells12212566
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author Runsala, Marika
Kuokkanen, Elina
Uski, Eveliina
Šuštar, Vid
Balci, Meryem Özge
Rajala, Johanna
Paavola, Vilma
Mattila, Pieta K.
author_facet Runsala, Marika
Kuokkanen, Elina
Uski, Eveliina
Šuštar, Vid
Balci, Meryem Özge
Rajala, Johanna
Paavola, Vilma
Mattila, Pieta K.
author_sort Runsala, Marika
collection PubMed
description In B cells, antigen processing and peptide-antigen (pAg) presentation is essential to ignite high-affinity antibody responses with the help of cognate T cells. B cells efficiently internalize and direct specific antigens for processing and loading onto MHCII. This critical step, which enables pAg presentation, occurs in MHCII compartments (MIICs) which possess the enzymatic machinery for pAg loading on MHCII. The intracellular transport systems that guide antigen and maintain this unique compartment remain enigmatic. Here, we probed the possible functional role of two known endosomal proteins, the Rab family small GTPases Rab7 and Rab9, that are both reported to colocalize with internalized antigen. As compared to Rab9, we found Rab7 to exhibit a higher overlap with antigen and MIIC components. Rab7 also showed a higher association with antigen degradation. The inhibition of Rab7 drastically decreased pAg presentation. Additionally, we detected the strong colocalization of perinuclearly clustered and presumably MIIC-associated antigen with autophagy protein LC3. When we pharmacologically inhibited autophagy, pAg presentation was inhibited. Together, our data promote Rab7 as an important regulator of antigen processing and, considering the previously reported functions of Rab7 in autophagy, this also raises the possibility of the involvement of autophagy-related machinery in this process.
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spelling pubmed-106493642023-11-02 The Small GTPase Rab7 Regulates Antigen Processing in B Cells in a Possible Interplay with Autophagy Machinery Runsala, Marika Kuokkanen, Elina Uski, Eveliina Šuštar, Vid Balci, Meryem Özge Rajala, Johanna Paavola, Vilma Mattila, Pieta K. Cells Article In B cells, antigen processing and peptide-antigen (pAg) presentation is essential to ignite high-affinity antibody responses with the help of cognate T cells. B cells efficiently internalize and direct specific antigens for processing and loading onto MHCII. This critical step, which enables pAg presentation, occurs in MHCII compartments (MIICs) which possess the enzymatic machinery for pAg loading on MHCII. The intracellular transport systems that guide antigen and maintain this unique compartment remain enigmatic. Here, we probed the possible functional role of two known endosomal proteins, the Rab family small GTPases Rab7 and Rab9, that are both reported to colocalize with internalized antigen. As compared to Rab9, we found Rab7 to exhibit a higher overlap with antigen and MIIC components. Rab7 also showed a higher association with antigen degradation. The inhibition of Rab7 drastically decreased pAg presentation. Additionally, we detected the strong colocalization of perinuclearly clustered and presumably MIIC-associated antigen with autophagy protein LC3. When we pharmacologically inhibited autophagy, pAg presentation was inhibited. Together, our data promote Rab7 as an important regulator of antigen processing and, considering the previously reported functions of Rab7 in autophagy, this also raises the possibility of the involvement of autophagy-related machinery in this process. MDPI 2023-11-02 /pmc/articles/PMC10649364/ /pubmed/37947644 http://dx.doi.org/10.3390/cells12212566 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Runsala, Marika
Kuokkanen, Elina
Uski, Eveliina
Šuštar, Vid
Balci, Meryem Özge
Rajala, Johanna
Paavola, Vilma
Mattila, Pieta K.
The Small GTPase Rab7 Regulates Antigen Processing in B Cells in a Possible Interplay with Autophagy Machinery
title The Small GTPase Rab7 Regulates Antigen Processing in B Cells in a Possible Interplay with Autophagy Machinery
title_full The Small GTPase Rab7 Regulates Antigen Processing in B Cells in a Possible Interplay with Autophagy Machinery
title_fullStr The Small GTPase Rab7 Regulates Antigen Processing in B Cells in a Possible Interplay with Autophagy Machinery
title_full_unstemmed The Small GTPase Rab7 Regulates Antigen Processing in B Cells in a Possible Interplay with Autophagy Machinery
title_short The Small GTPase Rab7 Regulates Antigen Processing in B Cells in a Possible Interplay with Autophagy Machinery
title_sort small gtpase rab7 regulates antigen processing in b cells in a possible interplay with autophagy machinery
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10649364/
https://www.ncbi.nlm.nih.gov/pubmed/37947644
http://dx.doi.org/10.3390/cells12212566
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