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The selectivity of cathepsin D suggests an involvement of the enzyme in the generation of T-cell epitopes

Author: Noort, J.M. van · Drift, A.C.M. van der
Type:article
Date:1989
Institution: Medisch Biologisch Laboratorium TNO
Source:Journal of Biological Chemistry, 24, 264, 14159-14164
Identifier: 230848
Keywords: Biology · Antigen · Cathepsin d · Animal cell · Antigen recognition · Cattle · Nonhuman · Protein processing · T lymphocyte · Amino Acid Sequence · Animal · Cathepsin D · Cattle · Epitopes · Hydrolysis · Molecular Sequence Data · Peptide Hydrolases · Pigeons · Sequence Homology, Nucleic Acid · Substrate Specificity · T-Lymphocytes · Whales

Abstract

The selectivity of cathepsin D, a mammalian intracellular aspartyl proteinase involved in the degradation of endocytosed proteins, was studied. For this purpose, several proteins of known primary structure were subjected to mild proteolysis by the enzyme, and the preferentially cleaved peptide bonds were identified. Comparison of the primary structures around these sites indicates that cathepsin D shows a strong preference for peptide bonds within a distinct sequence pattern of amino acids extending over 7 residues. In general, this pattern is most likely to occur within amphipathic α-helical structures. These findings and their possible implications are discussed together with additional evidence suggesting an important role for cathepsin D in the processing of protein antigens, an essential step for their recognition by T-cells. Accordingly, it is proposed that the proteolytic activity of cathepsin D is crucial in selecting processing sites and hence the location and structural context of T-cell epitopes for the majority of protein antigens. Chemicals/CAS: cathepsin D, 9025-26-7; Cathepsin D, EC 3.4.23.5; Epitopes; Peptide Hydrolases, EC 3.4