Natural processing sites for human cathepsin E and cathepsin D in tetanus toxin: implications for T cell epitope generation. 1997

E W Hewitt, and A Treumann, and N Morrice, and P J Tatnell, and J Kay, and C Watts
Department of Biochemistry, Medical Sciences Institute, University of Dundee, United Kingdom.

Cathepsin E is an aspartic proteinase that has been implicated frequently in Ag processing for presentation on class II MHC molecules, but no information exists on its cleavage specificity within Ags in relation to known T cell epitopes. We have analyzed the processing by cathepsin E of a large C-terminal domain of tetanus toxin (residues 872-1315), and we have compared the processing products with those liberated by cathepsin D, a related aspartic proteinase also thought to be involved in class II MHC-restricted Ag processing. Processing products were analyzed by N-terminal Edman degradation and mass spectrometry following reverse-phase HPLC separation of peptides. A total of 28 cleavage sites was identified, 11 of which were recognized by both cathepsins E and D. Most, although not all, sites were between pairs of hydrophobic residues and were located within the 200-amino-acid C terminal region known to contain several human T cell epitopes. Previously described T cell epitopes, for example, between residues 1273 and 1284, were flanked by cathepsin E and D cleavage sites. These data are consistent with an important role for cathepsins E and/or D in Ag processing in the human immune system.

UI MeSH Term Description Entries
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D010446 Peptide Fragments Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques. Peptide Fragment,Fragment, Peptide,Fragments, Peptide
D002402 Cathepsin D An intracellular proteinase found in a variety of tissue. It has specificity similar to but narrower than that of pepsin A. The enzyme is involved in catabolism of cartilage and connective tissue. EC 3.4.23.5. (Formerly EC 3.4.4.23).
D002403 Cathepsins A group of lysosomal proteinases or endopeptidases found in aqueous extracts of a variety of animal tissues. They function optimally within an acidic pH range. The cathepsins occur as a variety of enzyme subtypes including SERINE PROTEASES; ASPARTIC PROTEINASES; and CYSTEINE PROTEASES. Cathepsin
D002999 Clone Cells A group of genetically identical cells all descended from a single common ancestral cell by mitosis in eukaryotes or by binary fission in prokaryotes. Clone cells also include populations of recombinant DNA molecules all carrying the same inserted sequence. (From King & Stansfield, Dictionary of Genetics, 4th ed) Clones,Cell, Clone,Cells, Clone,Clone,Clone Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000595 Amino Acid Sequence The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION. Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D013601 T-Lymphocytes Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T Cell,T Lymphocyte,T-Cells,Thymus-Dependent Lymphocytes,Cell, T,Cells, T,Lymphocyte, T,Lymphocyte, Thymus-Dependent,Lymphocytes, T,Lymphocytes, Thymus-Dependent,T Cells,T Lymphocytes,T-Cell,T-Lymphocyte,Thymus Dependent Lymphocytes,Thymus-Dependent Lymphocyte
D013744 Tetanus Toxin Protein synthesized by CLOSTRIDIUM TETANI as a single chain of ~150 kDa with 35% sequence identity to BOTULINUM TOXIN that is cleaved to a light and a heavy chain that are linked by a single disulfide bond. Tetanolysin is the hemolytic and tetanospasmin is the neurotoxic principle. The toxin causes disruption of the inhibitory mechanisms of the CNS, thus permitting uncontrolled nervous activity, leading to fatal CONVULSIONS. Clostridial Neurotoxin,Clostridium tetani Toxin,Tetanus Toxins,Neurotoxin, Clostridial,Toxin, Clostridium tetani,Toxin, Tetanus,Toxins, Tetanus
D017951 Antigen Presentation The process by which antigen is presented to lymphocytes in a form they can recognize. This is performed by antigen presenting cells (APCs). Some antigens require processing before they can be recognized. Antigen processing consists of ingestion and partial digestion of the antigen by the APC, followed by presentation of fragments on the cell surface. (From Rosen et al., Dictionary of Immunology, 1989) Antigen Processing,Antigen Presentations,Antigen Processings

Related Publications

E W Hewitt, and A Treumann, and N Morrice, and P J Tatnell, and J Kay, and C Watts
December 1989, Journal of immunology (Baltimore, Md. : 1950),
E W Hewitt, and A Treumann, and N Morrice, and P J Tatnell, and J Kay, and C Watts
January 1995, Advances in experimental medicine and biology,
E W Hewitt, and A Treumann, and N Morrice, and P J Tatnell, and J Kay, and C Watts
September 1992, The International journal of biochemistry,
E W Hewitt, and A Treumann, and N Morrice, and P J Tatnell, and J Kay, and C Watts
December 2008, Biochemical and biophysical research communications,
E W Hewitt, and A Treumann, and N Morrice, and P J Tatnell, and J Kay, and C Watts
February 1997, The Journal of infectious diseases,
E W Hewitt, and A Treumann, and N Morrice, and P J Tatnell, and J Kay, and C Watts
October 1990, FEBS letters,
E W Hewitt, and A Treumann, and N Morrice, and P J Tatnell, and J Kay, and C Watts
November 1997, Vaccine,
E W Hewitt, and A Treumann, and N Morrice, and P J Tatnell, and J Kay, and C Watts
June 1996, Biochemical and biophysical research communications,
E W Hewitt, and A Treumann, and N Morrice, and P J Tatnell, and J Kay, and C Watts
January 2009, Methods in molecular biology (Clifton, N.J.),
E W Hewitt, and A Treumann, and N Morrice, and P J Tatnell, and J Kay, and C Watts
June 2007, The FEBS journal,
Copied contents to your clipboard!