Processing and presentation of insulin. III. Insulin degrading enzyme : A neutral metalloendoproteinase that is non-homologous to classical endoproteinases mediates the processing of insulin epitopes for helper T cells
(1992) In International Immunology 4(10). p.1161-1167- Abstract
Presentation of a protein antigen to T cells generally requires that the antigen be enzymatically processed into an immunogenic peptide(s). The identification of a protease(s) and its mechanism of action in the proteolysis of such an antigen is therefore a primary goal in the study of antigen processing. We show here that Insulin degrading enzyme (IDE), a neutral thiol metalloendo-proteinase that is structurally non-homologous to the classical metallo, thiol, acid, or serine proteinases, is relatively specific in its proteolytic activity for insulin and digests human insulin (HI) into peptides that are presented by murine TA3 B cell antigen presenting cells (APCs) to Hl/I-Ad-reactive T cells. These peptides are, however, not... (More)
Presentation of a protein antigen to T cells generally requires that the antigen be enzymatically processed into an immunogenic peptide(s). The identification of a protease(s) and its mechanism of action in the proteolysis of such an antigen is therefore a primary goal in the study of antigen processing. We show here that Insulin degrading enzyme (IDE), a neutral thiol metalloendo-proteinase that is structurally non-homologous to the classical metallo, thiol, acid, or serine proteinases, is relatively specific in its proteolytic activity for insulin and digests human insulin (HI) into peptides that are presented by murine TA3 B cell antigen presenting cells (APCs) to Hl/I-Ad-reactive T cells. These peptides are, however, not presented by fixed TA3 APCs. Anti-IDE mAbs, after their internalization by TA3 cells, significantly inhibit the presentation of HI by these APCs. Immunoblotting experiments demonstrate that this inhibition is mediated by the reactivity of these mAbs with a 110 kDa protein, the known Mr of IDE. These data show that IDE Is an endoprotelnase that is involved in the processing of insulin and that this IDE-mediated proteolysis is necessary but not sufficient for the recognition of insulin by T cells. Furthermore, we demonstrate that reduction of the disulfide bonds of a pre-processed A-loop containing heterodimeric insulin peptide is required to further process Insulin into a T cell epitope.
(Less)
- author
- Semple, John W. LU ; Lang, Ying ; Speck, Edwin R. and Delovitch, Terry L.
- publishing date
- 1992-10-01
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Antigen processing, B cell antigen presenting cells, Endoproteinase, Insulin
- in
- International Immunology
- volume
- 4
- issue
- 10
- pages
- 1161 - 1167
- publisher
- Oxford University Press
- external identifiers
-
- scopus:0026661263
- pmid:1283335
- ISSN
- 0953-8178
- DOI
- 10.1093/intimm/4.10.1161
- language
- English
- LU publication?
- no
- id
- b6d2fdd5-1cb8-4b0a-a184-c11a5e2aa910
- date added to LUP
- 2019-12-03 10:34:43
- date last changed
- 2024-01-02 01:35:33
@article{b6d2fdd5-1cb8-4b0a-a184-c11a5e2aa910,
abstract = {{<p>Presentation of a protein antigen to T cells generally requires that the antigen be enzymatically processed into an immunogenic peptide(s). The identification of a protease(s) and its mechanism of action in the proteolysis of such an antigen is therefore a primary goal in the study of antigen processing. We show here that Insulin degrading enzyme (IDE), a neutral thiol metalloendo-proteinase that is structurally non-homologous to the classical metallo, thiol, acid, or serine proteinases, is relatively specific in its proteolytic activity for insulin and digests human insulin (HI) into peptides that are presented by murine TA3 B cell antigen presenting cells (APCs) to Hl/I-A<sup>d</sup>-reactive T cells. These peptides are, however, not presented by fixed TA3 APCs. Anti-IDE mAbs, after their internalization by TA3 cells, significantly inhibit the presentation of HI by these APCs. Immunoblotting experiments demonstrate that this inhibition is mediated by the reactivity of these mAbs with a 110 kDa protein, the known M<sub>r</sub> of IDE. These data show that IDE Is an endoprotelnase that is involved in the processing of insulin and that this IDE-mediated proteolysis is necessary but not sufficient for the recognition of insulin by T cells. Furthermore, we demonstrate that reduction of the disulfide bonds of a pre-processed A-loop containing heterodimeric insulin peptide is required to further process Insulin into a T cell epitope.</p>}},
author = {{Semple, John W. and Lang, Ying and Speck, Edwin R. and Delovitch, Terry L.}},
issn = {{0953-8178}},
keywords = {{Antigen processing; B cell antigen presenting cells; Endoproteinase; Insulin}},
language = {{eng}},
month = {{10}},
number = {{10}},
pages = {{1161--1167}},
publisher = {{Oxford University Press}},
series = {{International Immunology}},
title = {{Processing and presentation of insulin. III. Insulin degrading enzyme : A neutral metalloendoproteinase that is non-homologous to classical endoproteinases mediates the processing of insulin epitopes for helper T cells}},
url = {{http://dx.doi.org/10.1093/intimm/4.10.1161}},
doi = {{10.1093/intimm/4.10.1161}},
volume = {{4}},
year = {{1992}},
}