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T cell recognition of naturally presented epitopes of self-heat shock protein 70

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Cell Stress and Chaperones Aims and scope

Abstract

Self-reactive T cells have shown to have a potential role as regulators of the immune system preventing or even suppressing autoimmunity. One of the most abundant proteins that can be eluted from human HLA molecules is heat shock protein 70 (HSP70). The aims of the current study are to identify HSP70 epitopes based on published HLA elution studies and to investigate whether T cells from healthy individuals may respond to such self-epitopes. A literature search and subsequent in silico binding prediction based on theoretical MHC binding motifs resulted in the identification of seven HSP70 epitopes. PBMCs of healthy controls proliferated after incubation with two of the seven peptides (H167 and H290). Furthermore H161, H290, and H443 induced CD69 expression or production of cytokines IFNγ or TNFα in healthy controls. The identification of these naturally presented epitopes and the response they elicit in the normal immune system make them potential candidates to study during inflammatory conditions as well as in autoimmune diseases.

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Authors and Affiliations

  1. Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands

    Huib de Jong & Johannes W. J. Bijlsma

  2. Laboratory of Translational Immunology, Department of Pediatric Immunology, University Medical Center Utrecht, Huispostnummer KE 04.131.1, Postbus 85090, 3508 AB, Utrecht, The Netherlands

    Huib de Jong, Eva C. Koffeman, Jennifer M. Meerding, Rianne C. Scholman, Wilco de Jager, Mark Klein, Femke van Wijk & Berent J. Prakken

  3. Department of Infectious Diseases and Immunology, Division of Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands

    Lotte Wieten, Ruurd van der Zee, Femke Broere & Willem van Eden

  4. Department of Immunology, University Medical Center Utrecht, 3508 GA, Utrecht, The Netherlands

    Henny Otten

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  1. Huib de Jong
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  2. Eva C. Koffeman
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Correspondence to Eva C. Koffeman.

Additional information

Huib de Jong and Eva C. Koffeman contributed equally to this study.

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Supplemental Figure A

Proliferation of donor PBMCs in response to the HSP70 peptides in relation to the HLA DR1 positivity and to the HLA DR4 positivity. Each dot represents an individual donor; means are shown per column. No differences could be found (Mann-Whitney test, all p values >0,05). (GIF 28 kb)

High-resolution image

(EPS 153 kb)

Supplemental Figure B

Expression of the combination of CD25 and FOXP3 and expression of LAP (TGF marker) by CD4+ T cells from short term T cells line restimulated with HSP70 peptides. Data are presented as percentage of CD3+ CD4+ cells positive for the staining, with the background (unstimulated condition) subtracted. Each dot represents an individual donor, mean is shown per column. (GIF 18 kb)

High-resolution image

(EPS 65 kb)

Supplemental Figure C

Percentage of CD45RO positive cells within the population of CD69 or cytokine positive CD4+ T cells. Each dot represents an individual donor, mean is shown per column. (GIF 31 kb)

High-resolution image

(EPS 93 kb)

Supplemental Figure D

Dot plots of two samples from donors with clear cytokine response by T cells, showing % CD45RO positivity within the population of CD69 or cytokine positive CD4+ T cells. (JPEG 41 kb)

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(TIFF 82 kb)

Supplemental Figure E

CD4 and CD8 staining of CD3+ cells from short term T cell lines restimulated with HSP70 peptides, showing the expression of CD69 and production of IFN and TNF in the two T cell subsets. Data are presented as percentage of CD3+ CD4+/CD8+ cells positive for the staining, with the background (unstimulated condition) subtracted. Each dot represents an individual donor, mean is shown per column. (GIF 31 kb)

High-resolution image

(EPS 147 kb)

Supplemental Figure F

Production of IFN by CD3− CD56+ cells from the short term culture restimulated with HSP70 peptides. Data are presented as percentage of CD3− CD56+ cells positive for the staining, with the background (unstimulated condition) subtracted. Each dot represents an individual donor, mean is shown per column. (GIF 5 kb)

High-resolution image

(EPS 58 kb)

Supplemental Figure G

Expression of CD69 and production of IFN, IL-10 and TNF by CD3+CD4+ T cells from short term T cells line restimulated with HSP70 peptides. Data are presented as Geo Mean of the positive cells. Each dot represents an individual donor, mean is shown per column. (GIF 13 kb)

High-resolution image

(EPS 90 kb)

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de Jong, H., Koffeman, E.C., Meerding, J.M. et al. T cell recognition of naturally presented epitopes of self-heat shock protein 70. Cell Stress and Chaperones 19, 569–578 (2014). https://doi.org/10.1007/s12192-013-0484-1

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