Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We find that expression of the membrane dipeptidyl carboxypeptidase angiotensin-converting enzyme (ACE) enhances presentation of certain endogenously synthesized peptides to major histocompatibility complex (MHC) class I-restricted cytotoxic T lymphocytes. ACE appears to function only in an intracellular secretory compartment of antigen-presenting cells. ACE-enhanced antigen presentation requires the expression of the putative antigenic peptide transporters, TAP1 and TAP2. These findings demonstrate that a protease can influence the processing of endogenously synthesized antigens and strongly suggest that longer peptides can be transported from the cytosol to a secretory compartment where trimming of antigenic peptides to the lengths preferred by MHC class I molecules can occur if the appropriate protease is present.
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PMID:Expression of a membrane protease enhances presentation of endogenous antigens to MHC class I-restricted T lymphocytes. 133 89

These perspectives from the first International Symposium on Primary Biliary Cirrhosis review recent advances and single out some areas for further enquiry. The latter include frequency and type of associated autoimmune diseases, the existence of clinical subsets of PBC, immunohistochemical analysis of lymphoid infiltrates in the liver, effects of immunosuppressive and other treatment regimens, and models for predicting the optimal time for liver transplantation. The M2 autoantigens have been identified as mitochondrial 2-oxo-acid dehydrogenase enzymes. These include pyruvate dehydrogenase (70-74 kd antigen) and branched chain 2-oxo-acid dehydrogenase and 2-oxo-acid glutaric dehydrogenase (45-52 kd antigens). Each of these enzymes has three subunits, E1 to E3. For PDH, an autoepitope has been identified as a decapeptide containing the attachment site of lipoic acid, an essential cofactor for enzyme activity. Current questions include the degree to which antibodies to PDH, and related enzymes, account for the mitochondrial reactivity defined by immunofluorescence or other procedures, the cell-surface expression of M2 autoantigens, and the significance of the occurrence of nonmitochondrial (such as centromeric) autoantibodies in PBC. The unknown T lymphocyte contribution to the autoimmune response in PBC may involve inducer and effector components. A postulated T-cell autoepitope may be presented, in association with MHC class I or class II molecules, on the surface of biliary epithelial cells. T cell lines from PBC livers removed during transplantation could provide data on the T-lymphocyte contribution to the pathogenesis of PBC.
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PMID:Primary biliary cirrhosis: current knowledge, perspectives, and future directions. 265 6

In this study the immunogenic tryptic fragment from a horse cytochrome c (cyt c) digest recognized by cytotoxic T lymphocytes (CTL) induced by in vitro peptide stimulation from C57BL/6 (B6) and mutant B6.C-H-2bm1 (bm1) mice is identified. An identical sequence, p40-53, is recognized by CTL from both B6 and bm1 mice. In addition, both B6 bm1 cloned CTL lines display unusual major histocompatibility complex (MHC) class I-restricted recognition of this peptide in that they respond to it in the context of H-2Kb, H-2Db, and H-2Kbm1 class I molecules, although the sequence lacks the usual structural Kb and Db peptide-binding motifs. Truncated analogues which resemble the lengths of naturally processed MHC class I-presented peptides, confer reactivity for B6 and bm1 CTL against EL4 (H-2b) targets as well as the L cell transfectants, L+Kb, L+Db, and L+Kbm1. The antigenic peptide with the greatest potency is p41-49, which appears to be generated by angiotensin converting enzyme cleavage of the full-length p40-53 tryptic peptide. The minimum antigenic peptide recognized by both B6 and bm1 CTL, and which targets lysis on each of the transfectants, is the hexamer p43-48 peptide from horse cyt c. Residues Pro44 and Thr47, which occupy polymorphic positions with respect to other species-variant cyt c molecules, influence recognition of these peptides differently for the B6 and bm1 CTL. The ability of H-2Kb, H-2Db, and mutant H-2Kbm1 class I molecules to present the same peptide to a single cloned CTL is discussed in the context of current knowledge of peptide anchor residues and side chain-specific binding pockets in the MHC class I peptide-binding site.
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PMID:Presentation of a horse cytochrome c peptide by multiple H-2b class I major histocompatibility complex (MHC) molecules to C57BL/6- and bm1-derived cytotoxic T lymphocytes: presence of a single MHC anchor residue may confer efficient peptide-specific CTL recognition. 752 63