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Contribution of proteasome-mediated proteolysis to the hierarchy of epitopes presented by major histocompatibility complex class I molecules

Identifieur interne : 004095 ( Main/Exploration ); précédent : 004094; suivant : 004096

Contribution of proteasome-mediated proteolysis to the hierarchy of epitopes presented by major histocompatibility complex class I molecules

Auteurs : Gabrlele Niedermann [Allemagne] ; Stefan Butz [Allemagne] ; Hans Georg Ihlenfeldt [Allemagne] ; Rudolf Grimm [Allemagne] ; Maria Lucchlarl [Allemagne] ; Heinz Hoschotzky [Allemagne] ; Günther Jung [Allemagne] ; Bernhard Maier [Allemagne] ; Klaus Elchmann [Allemagne]

Source :

RBID : ISTEX:9F4C5E332350C244442AB2E86E43D7595D2A2E61

English descriptors

Abstract

Abstract: Major histocompatibility complex (MHC) class I-restricted cytotoxic T lymphocytes (CTL) recognize peptide epitopes of protein antigens in a hierarchical fashion. We investigated whether proteolytic cleavage, in particular by proteasomes, Is important in determining epitope hierarchy. Using highly purified 20S proteasomes, we find preferred cleavage sites directly adjacent to the N- and C-terminal ends of the immunodominant epitope of chicken ovalbumin, Ova257–264, while most of the subdominant epitope, Ova55–62, is destroyed by a major cleavage site located within this epitope. Moreover, we show that variations in amino acid sequences flanking these epitopes influence proteasomal cleavage patterns In parallel with the efficacy of their presentation. The results suggest that proteasomal cleavage within and adjacent to class I-restricted epitopes contributes to their level of presentation.

Url:
DOI: 10.1016/1074-7613(95)90053-5


Affiliations:


Links toward previous steps (curation, corpus...)


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<div type="abstract" xml:lang="en">Abstract: Major histocompatibility complex (MHC) class I-restricted cytotoxic T lymphocytes (CTL) recognize peptide epitopes of protein antigens in a hierarchical fashion. We investigated whether proteolytic cleavage, in particular by proteasomes, Is important in determining epitope hierarchy. Using highly purified 20S proteasomes, we find preferred cleavage sites directly adjacent to the N- and C-terminal ends of the immunodominant epitope of chicken ovalbumin, Ova257–264, while most of the subdominant epitope, Ova55–62, is destroyed by a major cleavage site located within this epitope. Moreover, we show that variations in amino acid sequences flanking these epitopes influence proteasomal cleavage patterns In parallel with the efficacy of their presentation. The results suggest that proteasomal cleavage within and adjacent to class I-restricted epitopes contributes to their level of presentation.</div>
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