title: Link between organ-specific antigen processing by 20S proteasomes and CD8(+) T cell-mediated autoimmunity.
abstract: Adoptive transfer of cross-reactive HSP60-specific CD8(+) T cells into immunodeficient mice causes autoimmune intestinal pathology restricted to the small intestine. We wondered whether local immunopathology induced by CD8(+) T cells can be explained by tissue-specific differences in proteasome-mediated processing of major histocompatibility complex class I T cell epitopes. Our experiments demonstrate that 20S proteasomes of different organs display a characteristic composition of alpha and beta chain subunits and produce distinct peptide fragments with respect to both quality and quantity. Digests of HSP60 polypeptides by 20S proteasomes show most efficient generation of the pathology related CD8(+) T cell epitope in the small intestine. Further, we demonstrate that the organ-specific potential to produce defined T cell epitopes reflects quantities that are relevant for cytotoxic T lymphocyte recognition. We propose tissue-specific antigen processing by 20S proteasomes as a potential mechanism to control organ-specific immune responses.
authors.affiliation: Institute of Biochemistry, Charite, Humboldt University, D-10117 Berlin, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Kuckelkorn
authors.forename: Thomas
authors.initials: T
authors.lastname: Ruppert
authors.forename: Britta
authors.initials: B
authors.lastname: Strehl
authors.forename: Peter R
authors.initials: PR
authors.lastname: Jungblut
authors.forename: Ursula
authors.initials: U
authors.lastname: Zimny-Arndt
authors.forename: Stephanie
authors.initials: S
authors.lastname: Lamer
authors.forename: Immo
authors.initials: I
authors.lastname: Prinz
authors.forename: Ilse
authors.initials: I
authors.lastname: Drung
authors.forename: Peter-M
authors.initials: PM
authors.lastname: Kloetzel
authors.forename: Stefan H E
authors.initials: SH
authors.lastname: Kaufmann
authors.forename: Ulrich
authors.initials: U
authors.lastname: Steinhoff
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018834:Chaperonin 60 / Q000276:immunology; D003546:Cysteine Endopeptidases / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D007421:Intestine, Small / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D046988:Proteasome Endopeptidase Complex; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D018834:Chaperonin 60; D018984:Epitopes, T-Lymphocyte; D009097:Multienzyme Complexes; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex