Destructive proteolysis by cysteine proteases in antigen presentation of ovalbumin

Gloria Rodriguez, Stephanie Dimen

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

Most native antigens require digestion by acidic proteases in order to be recognized in the context of major histocompatibility complex class II by T helper cells (Th). We have studied the roles of three different acidic proteases, cathepsin D, cathepsin B and cathepsin L, in the processing of ovalbumin (OVA) for presentation in the context of I‐Ad. We report that digestion of OVA in vitro with the aspartyl protease cathepsin D generates the epitope OVA322–336, which is recognized by I‐Ad‐restricted OVA‐specific Th in the presence of paraformaldehyde‐fixed antigen‐presenting cells (APC). In contrast, digestion of OVA with the cysteine proteases cathepsin B and L not only failed to generate an epitope, but also destroyed OVA322–336. In the presence of fixed APC expressing I‐Ad, OVA322–336 was protected from destructive proteolysis by cathepsin L. These results illustrate the dependence of epitope selection on the intracellular proteolytic environment in APC, and suggest that mechanisms must exist for protection of epitopes from destructive proteolysis in the processing compartments.

Original languageEnglish (US)
Pages (from-to)1823-1827
Number of pages5
JournalEuropean Journal of Immunology
Volume25
Issue number7
DOIs
StatePublished - Jan 1 1995

Fingerprint

Cysteine Proteases
Ovalbumin
Antigen Presentation
Cathepsin L
Proteolysis
Epitopes
Digestion
Cathepsin B
Cathepsin D
Helper-Inducer T-Lymphocytes
Peptide Hydrolases
Aspartic Acid Proteases
Major Histocompatibility Complex
Antigens

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Keywords

  • Cathepsin B
  • Cathepsin D
  • Cathepsin L
  • Major histocompatibility complex class II

Cite this

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abstract = "Most native antigens require digestion by acidic proteases in order to be recognized in the context of major histocompatibility complex class II by T helper cells (Th). We have studied the roles of three different acidic proteases, cathepsin D, cathepsin B and cathepsin L, in the processing of ovalbumin (OVA) for presentation in the context of I‐Ad. We report that digestion of OVA in vitro with the aspartyl protease cathepsin D generates the epitope OVA322–336, which is recognized by I‐Ad‐restricted OVA‐specific Th in the presence of paraformaldehyde‐fixed antigen‐presenting cells (APC). In contrast, digestion of OVA with the cysteine proteases cathepsin B and L not only failed to generate an epitope, but also destroyed OVA322–336. In the presence of fixed APC expressing I‐Ad, OVA322–336 was protected from destructive proteolysis by cathepsin L. These results illustrate the dependence of epitope selection on the intracellular proteolytic environment in APC, and suggest that mechanisms must exist for protection of epitopes from destructive proteolysis in the processing compartments.",
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Destructive proteolysis by cysteine proteases in antigen presentation of ovalbumin. / Rodriguez, Gloria; Dimen, Stephanie.

In: European Journal of Immunology, Vol. 25, No. 7, 01.01.1995, p. 1823-1827.

Research output: Contribution to journalArticle

TY - JOUR

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AU - Rodriguez, Gloria

AU - Dimen, Stephanie

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N2 - Most native antigens require digestion by acidic proteases in order to be recognized in the context of major histocompatibility complex class II by T helper cells (Th). We have studied the roles of three different acidic proteases, cathepsin D, cathepsin B and cathepsin L, in the processing of ovalbumin (OVA) for presentation in the context of I‐Ad. We report that digestion of OVA in vitro with the aspartyl protease cathepsin D generates the epitope OVA322–336, which is recognized by I‐Ad‐restricted OVA‐specific Th in the presence of paraformaldehyde‐fixed antigen‐presenting cells (APC). In contrast, digestion of OVA with the cysteine proteases cathepsin B and L not only failed to generate an epitope, but also destroyed OVA322–336. In the presence of fixed APC expressing I‐Ad, OVA322–336 was protected from destructive proteolysis by cathepsin L. These results illustrate the dependence of epitope selection on the intracellular proteolytic environment in APC, and suggest that mechanisms must exist for protection of epitopes from destructive proteolysis in the processing compartments.

AB - Most native antigens require digestion by acidic proteases in order to be recognized in the context of major histocompatibility complex class II by T helper cells (Th). We have studied the roles of three different acidic proteases, cathepsin D, cathepsin B and cathepsin L, in the processing of ovalbumin (OVA) for presentation in the context of I‐Ad. We report that digestion of OVA in vitro with the aspartyl protease cathepsin D generates the epitope OVA322–336, which is recognized by I‐Ad‐restricted OVA‐specific Th in the presence of paraformaldehyde‐fixed antigen‐presenting cells (APC). In contrast, digestion of OVA with the cysteine proteases cathepsin B and L not only failed to generate an epitope, but also destroyed OVA322–336. In the presence of fixed APC expressing I‐Ad, OVA322–336 was protected from destructive proteolysis by cathepsin L. These results illustrate the dependence of epitope selection on the intracellular proteolytic environment in APC, and suggest that mechanisms must exist for protection of epitopes from destructive proteolysis in the processing compartments.

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