Invariant chain processing is independent of cathepsin variation between primary human B cells/dendritic cells and B-lymphoblastoid cells

Michael Reich, Fang Zou, Marcin Sieńczyk, Jozef Oleksyszyn, Bernhard O Boehm, Timo Burster

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

As part of the endocytic antigen processing pathway, proteolytic cleavage of the invariant chain (Ii) is important for the generation of class II-associated invariant chain peptide (CLIP). CLIP remains associated with the major histocompatibility complex (MHC) class II molecule to prevent premature loading of antigenic peptides. Cysteine proteases, such as Cathepsin S (CatS), CatL, or CatV, play a pivotal role in the final stage of Ii degradation depending on the cell type studied. Less is known regarding the early stages of Ii processing. We therefore explored whether the serine protease CatG is involved in the initial step of Ii degradation in primary antigen presenting cells (APC), since the cathepsin distribution differs between primary APC and cell lines. While primary human B cells and dendritic cells (DC) do harbor CatG, this protease is absent in B-lymphoblastoid cells (BLC) or monocyte-derived DC generated in vitro. In addition, other proteases, such as CatC, CatL, and the asparagine endoprotease (AEP), are active in BLC and monocyte-derived DC. Here we demonstrate that CatG progressively degraded Ii in vitro resulting in several intermediates. However, pharmacological inhibition of CatG in primary B cells and DC did not alter Ii processing, indicating that CatG is dispensable in Ii degradation. Interestingly, stalling of cysteine proteases by inhibition in BLC vs. primary B cells and DC did not result in any differences in the generation of distinct Ii intermediates between the cells tested, suggesting that Ii processing is independent of the cathepsin variation within professional human APC.

Original languageEnglish
Pages (from-to)96-103
Number of pages8
JournalCellular Immunology
Volume269
Issue number2
DOIs
Publication statusPublished - 2011

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Cathepsins
Dendritic Cells
B-Lymphocytes
Antigen-Presenting Cells
cathepsin S
Cysteine Proteases
Monocytes
Peptide Hydrolases
Asparagine
Antigen Presentation
Serine Proteases
Major Histocompatibility Complex
Cats
invariant chain
Pharmacology
Cell Line
Peptides

Keywords

  • Antigens, Differentiation, B-Lymphocyte
  • B-Lymphocytes
  • Cathepsin G
  • Cathepsins
  • Cell Extracts
  • Cell Line, Transformed
  • Cell-Free System
  • Cysteine Proteinase Inhibitors
  • Dendritic Cells
  • Histocompatibility Antigens Class II
  • Humans
  • Hydrogen-Ion Concentration
  • Leukocytes, Mononuclear
  • Recombinant Proteins
  • Serine Proteinase Inhibitors
  • Journal Article
  • Research Support, Non-U.S. Gov't

Cite this

Invariant chain processing is independent of cathepsin variation between primary human B cells/dendritic cells and B-lymphoblastoid cells. / Reich, Michael; Zou, Fang; Sieńczyk, Marcin; Oleksyszyn, Jozef; Boehm, Bernhard O; Burster, Timo.

In: Cellular Immunology, Vol. 269, No. 2, 2011, p. 96-103.

Research output: Contribution to journalArticle

Reich, Michael ; Zou, Fang ; Sieńczyk, Marcin ; Oleksyszyn, Jozef ; Boehm, Bernhard O ; Burster, Timo. / Invariant chain processing is independent of cathepsin variation between primary human B cells/dendritic cells and B-lymphoblastoid cells. In: Cellular Immunology. 2011 ; Vol. 269, No. 2. pp. 96-103.
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abstract = "As part of the endocytic antigen processing pathway, proteolytic cleavage of the invariant chain (Ii) is important for the generation of class II-associated invariant chain peptide (CLIP). CLIP remains associated with the major histocompatibility complex (MHC) class II molecule to prevent premature loading of antigenic peptides. Cysteine proteases, such as Cathepsin S (CatS), CatL, or CatV, play a pivotal role in the final stage of Ii degradation depending on the cell type studied. Less is known regarding the early stages of Ii processing. We therefore explored whether the serine protease CatG is involved in the initial step of Ii degradation in primary antigen presenting cells (APC), since the cathepsin distribution differs between primary APC and cell lines. While primary human B cells and dendritic cells (DC) do harbor CatG, this protease is absent in B-lymphoblastoid cells (BLC) or monocyte-derived DC generated in vitro. In addition, other proteases, such as CatC, CatL, and the asparagine endoprotease (AEP), are active in BLC and monocyte-derived DC. Here we demonstrate that CatG progressively degraded Ii in vitro resulting in several intermediates. However, pharmacological inhibition of CatG in primary B cells and DC did not alter Ii processing, indicating that CatG is dispensable in Ii degradation. Interestingly, stalling of cysteine proteases by inhibition in BLC vs. primary B cells and DC did not result in any differences in the generation of distinct Ii intermediates between the cells tested, suggesting that Ii processing is independent of the cathepsin variation within professional human APC.",
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T1 - Invariant chain processing is independent of cathepsin variation between primary human B cells/dendritic cells and B-lymphoblastoid cells

AU - Reich, Michael

AU - Zou, Fang

AU - Sieńczyk, Marcin

AU - Oleksyszyn, Jozef

AU - Boehm, Bernhard O

AU - Burster, Timo

N1 - Copyright © 2011 Elsevier Inc. All rights reserved.

PY - 2011

Y1 - 2011

N2 - As part of the endocytic antigen processing pathway, proteolytic cleavage of the invariant chain (Ii) is important for the generation of class II-associated invariant chain peptide (CLIP). CLIP remains associated with the major histocompatibility complex (MHC) class II molecule to prevent premature loading of antigenic peptides. Cysteine proteases, such as Cathepsin S (CatS), CatL, or CatV, play a pivotal role in the final stage of Ii degradation depending on the cell type studied. Less is known regarding the early stages of Ii processing. We therefore explored whether the serine protease CatG is involved in the initial step of Ii degradation in primary antigen presenting cells (APC), since the cathepsin distribution differs between primary APC and cell lines. While primary human B cells and dendritic cells (DC) do harbor CatG, this protease is absent in B-lymphoblastoid cells (BLC) or monocyte-derived DC generated in vitro. In addition, other proteases, such as CatC, CatL, and the asparagine endoprotease (AEP), are active in BLC and monocyte-derived DC. Here we demonstrate that CatG progressively degraded Ii in vitro resulting in several intermediates. However, pharmacological inhibition of CatG in primary B cells and DC did not alter Ii processing, indicating that CatG is dispensable in Ii degradation. Interestingly, stalling of cysteine proteases by inhibition in BLC vs. primary B cells and DC did not result in any differences in the generation of distinct Ii intermediates between the cells tested, suggesting that Ii processing is independent of the cathepsin variation within professional human APC.

AB - As part of the endocytic antigen processing pathway, proteolytic cleavage of the invariant chain (Ii) is important for the generation of class II-associated invariant chain peptide (CLIP). CLIP remains associated with the major histocompatibility complex (MHC) class II molecule to prevent premature loading of antigenic peptides. Cysteine proteases, such as Cathepsin S (CatS), CatL, or CatV, play a pivotal role in the final stage of Ii degradation depending on the cell type studied. Less is known regarding the early stages of Ii processing. We therefore explored whether the serine protease CatG is involved in the initial step of Ii degradation in primary antigen presenting cells (APC), since the cathepsin distribution differs between primary APC and cell lines. While primary human B cells and dendritic cells (DC) do harbor CatG, this protease is absent in B-lymphoblastoid cells (BLC) or monocyte-derived DC generated in vitro. In addition, other proteases, such as CatC, CatL, and the asparagine endoprotease (AEP), are active in BLC and monocyte-derived DC. Here we demonstrate that CatG progressively degraded Ii in vitro resulting in several intermediates. However, pharmacological inhibition of CatG in primary B cells and DC did not alter Ii processing, indicating that CatG is dispensable in Ii degradation. Interestingly, stalling of cysteine proteases by inhibition in BLC vs. primary B cells and DC did not result in any differences in the generation of distinct Ii intermediates between the cells tested, suggesting that Ii processing is independent of the cathepsin variation within professional human APC.

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KW - Cell Line, Transformed

KW - Cell-Free System

KW - Cysteine Proteinase Inhibitors

KW - Dendritic Cells

KW - Histocompatibility Antigens Class II

KW - Humans

KW - Hydrogen-Ion Concentration

KW - Leukocytes, Mononuclear

KW - Recombinant Proteins

KW - Serine Proteinase Inhibitors

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

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DO - 10.1016/j.cellimm.2011.03.012

M3 - Article

VL - 269

SP - 96

EP - 103

JO - Cellular Immunology

JF - Cellular Immunology

SN - 0008-8749

IS - 2

ER -