title: T cell recognition of naturally presented epitopes of self-heat shock protein 70.
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.
authors.affiliation: Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Huib
authors.initials: H
authors.lastname: de Jong
authors.forename: Eva C
authors.initials: EC
authors.lastname: Koffeman
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Meerding
authors.forename: Rianne C
authors.initials: RC
authors.lastname: Scholman
authors.forename: Lotte
authors.initials: L
authors.lastname: Wieten
authors.forename: Wilco
authors.initials: W
authors.lastname: de Jager
authors.forename: Mark
authors.initials: M
authors.lastname: Klein
authors.forename: Henny
authors.initials: H
authors.lastname: Otten
authors.forename: Femke
authors.initials: F
authors.lastname: van Wijk
authors.forename: Ruurd
authors.initials: R
authors.lastname: van der Zee
authors.forename: Johannes W J
authors.initials: JW
authors.lastname: Bijlsma
authors.forename: Femke
authors.initials: F
authors.lastname: Broere
authors.forename: Willem
authors.initials: W
authors.lastname: van Eden
authors.forename: Berent J
authors.initials: BJ
authors.lastname: Prakken
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D015551:Autoimmunity; D002460:Cell Line; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D018984:Epitopes, T-Lymphocyte; D005260:Female; D005802:Genes, MHC Class II; D018840:HSP70 Heat-Shock Proteins / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D008297:Male; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D055815:Young Adult
chemical_list: D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D018840:HSP70 Heat-Shock Proteins; D010455:Peptides