Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.1 (chymotrypsin)
 10,938 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Highly purified, papain-solubilized HLA-A, -B, and -C antigens comprising a mixture of a great number of allelic forms from at least three loci have been fragmented by limited proteolysis, acid cleavage, and cyanogen bromide treatment. Limited proteolysis of 125I-labeled HLA-A, -B, and -C antigens with trypsin, chymotrypsin, thermolysin, and pepsin resulted in the production of two large fragments. One fragment was associated with beta 2-microglobulin and contained all of the carbohydrate. The other fragment, which had a molecular weight of about 13,000, is most probably derived from the COOH-terminal part of the heavy chain. Acid cleavage of the HLA antigen heavy chain gave rise to two main fragments with molecular weights of 22,000 and 11,000. Both fragments contained disulfide bonds. Two minor components, representing further cleavage products of the 22,000-dalton fragment, were also observed. Cleavage of the HLA antigen heavy chain at methionyl residues gave rise to one carbohydrate-containing, cysteine-free 14,000-dalton fragment and one 20,000-dalton fragment that contained all cysteines but no carbohydrate. NH2-terminal amino acid sequence analyses demonstrated that the 22,000-dalton acid cleavage fragment and the 14,000-dalton cyanogen bromide fragment were derived from the NH2-terminal part of the HLA antigen heavy chain.
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PMID:Fragmentation of the human transplantation antigen heavy chain by limited proteolysis, acid cleavage, and cyanogen bromide treatment. 37 76

Using immunohistochemical techniques and a large number of monoclonal antibodies, the presence and distribution of phenotypic subpopulations of macrophages (MOs) and dendritic cells in human spleen were assessed. The results of this study show that different subsets of MOs and dendritic cells are present in the spleen and that some of these occupy discrete microanatomic locations. In the red pulp (RP) certain antigens are expressed by different proportions of uniformly distributed MOs in the cords. On the other hand, some antigens are present on MOs that form clusters of variable size within the red pulp. These include CD11c, CD15 and alpha-1-anti-chymotrypsin. Another type of cell in the RP that is phagocytic under certain conditions is the splenic sinusoidal lining cell (SLC). These cells exhibit a phenotype that is unique: nonspecific esterase (NSE)+, lysozyme+, and HLA-DR+, CD36+, factor VIII-related antigen+, CD8+ and CD71+. MOs in the splenic marginal zone (MZ) share some antigens with red pulp MOs, but in addition express CD11b, CD14 (Mo2;63D3) and 61D3. These antigens are found on only a few RP MOs. MZ cells expressing one antigen shared with RP MOs (CD4) and one present largely on the MZ cells (CD14;63D3) form clusters around small vessels; these structures resemble the so-called splenic ellipsoids that may play a role in the trapping of circulating antigens. Phagocytic MOs (tangible body MOs) of the white pulp follicular germinal centers were also shown to differ from RP and MZ cells with respect to the expression of the antigens CD11b, CD14 (Leu M3;Mo2), CD16 and the antigen detected by antibody 25F9. The unique topographical and surface antigenic features of dendritic cells were confirmed by this study. Furthermore, these cells were found to share a number of antigens with RP, MZ, and white pulp MOs, which suggests that they may be derived from a common progenitor. The presence of phenotypic subpopulations and variation in distribution among human splenic phagocytic cells and dendritic cells may be indicative of functional specialization.
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PMID:Phenotypic subpopulations of macrophages and dendritic cells in human spleen. 205 20

A new cell line DEL, established in vitro, was isolated from a pleural effusion of a boy who died of malignant histiocytosis. Its principal characteristics are: strong positivity with monoclonal antibodies (MAbs) to CD25, CD30, CD45R, KiM7, EMA, HLA Cl I and II; constant presence of acid phosphatase, ANAE, alpha-anti-trypsin, alpha-anti-chymotrypsin and NBT reductase activity; rearrangement of the immunoglobulin heavy-chain gene (JH) and a germ-line configuration of the T-chain gene; and finally a translocation between chromosomes 5-6 with a breakpoint in 5q35. The DEL cell line is appropriate for studying the role of the 5q localized c-fms oncogene and of the genes of the mononuclear phagocyte growth factor (CSFI) and of their receptors in the dynamics and etiology of malignant hemopathies associated with a 5q35 breakpoint.
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PMID:DEL cell line: a "malignant histiocytosis" CD30+ t(5;6)(q35;p21) cell line. 230 42

A human hepatoma cell line, associated with thorotrast exposure, from an hepatitis B marker-negative patient was established as a permanent cell line (Mz-Hep-1) in tissue culture. Histology of the primary tumor, as well as phase contrast, transmission and scanning electron microscopy of the cultured cells showed typical characteristics of liver cells. Mz-Hep-1 cells secreted complement components (C2, C3, C4), carcinoembryonic antigen, lactate dehydrogenase, chymotrypsin, haptoglobin and retinol-binding protein and expressed HLA-, transferrin-, blood group B-related determinants and complement component C5 and carcinoembryonic antigen on their cell surface. Mz-Hep-1 cells represent the first human hepatoma cell line, which is strongly associated with a carcinogen.
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PMID:Hepatocellular carcinoma after thorotrast exposure: establishment of a new cell line (Mz-Hep-1). 241 35

Lymphocytes were treated with hydrolytic enzymes primarily to assess whether such modified cells would give improved cytotoxicity reactions during tissue typing. Papain-treated and alpha-chymotrypsin-treated lymphocytes were approximately twice as sensitive as untreated cells in the microcytotoxicity test used, and this finding might be usefully exploited by immunological laboratories for purposes of cross-matching, HLA antibody screening and HLA-DR typing. Trypsin treatment promoted massive cell clumping, while neuraminidase treatment was responsible for indiscriminate cell death after exposure to rabbit serum. The capacity of lymphocytes to form rosettes with sheep erythrocytes was abolished after treatment with trypsin or alpha-chymotrypsin, but enhanced by papain or neuraminidase.
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PMID:Enzymatic modification of the lymphocyte surface. Application to tissue typing and rosetting with sheep erythrocytes. 657 19

The effects of the inhibitor of N-linked glycosylation, tunicamycin, on the synthesis of HLA-A and -B antigens in the human lymphoblastoid cell line JY are described. HLA-A and -B antigens are membrane glycoproteins that consist of a two chain complex, the heavy chain being glycosylated at Asn 86, whereas the light chain, identical to beta 2-microglobulin, is not glycosylated. HLA-A and -B antigens synthesized in the presence of the antibiotic are devoid of carbohydrate. This lack of carbohydrate does not affect the association of the heavy and light chains, nor does it affect the reactivity with human alloantisera, or a mouse monoclonal antibody W6/32, that reacts with all HLA-A and -B specificities examined so far. Nonglycosylated HLA-A and -B antigens are no more susceptible to proteolysis with trypsin, chymotrypsin, or papain than their fully glycosylated counterparts. Thus it may be concluded that the carbohydrate side chains of HLA-A and -B antigens do not contribute significantly to the conformation of HLA-A and -B antigens, at least as measured by these procedures. Pulse-chase experiments, in conjunction with the isolation of cell-surface HLA-A and -B antigens by adsorbing the monoclonal antibody W6/32 to intact cells, indicate that nonglycosylated molecules reach the cell surface at a rate indistinguishable from that of fully glycosylated molecules (although the absolute amount synthesized in the presence of tunicamycin was decreased). Thus glycosylation is also not required for membrane insertion of HLA antigens, nor for their subsequent transport to the cell surface.
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PMID:Biosynthesis and cell surface localization of nonglycosylated human histocompatibility antigens. 700 35

Celiac disease is an HLA-DQ2-associated disorder characterized by intestinal T cell responses to ingested wheat gliadins. Initial studies used gliadin that had been subjected to non-enzymatic deamidation during pepsin/trypsin digestion to enrich for the gliadin-specific T cells in small intestinal celiac biopsies. These T cells recognized synthetic gliadin peptides only after their deamidation in vitro by purified tissue transglutaminase (tTG). However, as these studies used a deamidated antigen for re-stimulation prior to testing for antigen specificity, this raised the possibility that T cells specific for native epitopes had not been expanded in vitro and had thus been overlooked. To address this possibility and to look for more direct evidence that endogenous tTG mediates deamidation of gluten in the celiac lesions, we have here used a minimally deamidated chymotrypsin-digest of gliadin to challenge biopsies and then investigated the specificity of the T cell lines derived from them. Interestingly, these T cell lines only barely responded to the chymotrypsin-digested gliadins, but efficiently recognized the in vitro tTG-treated variants of the same gliadins. Moreover, the addition of a tTG-inhibitor during the gliadin challenge often resulted in T cell lines with abolished or reduced responses to deamidated gliadin. These data demonstrate that DQ2-restricted T cells within adult celiac lesions predominantly recognize deamidated gliadin epitopes that are formed in situ by endogenous tTG.
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PMID:T cells from celiac disease lesions recognize gliadin epitopes deamidated in situ by endogenous tissue transglutaminase. 1146 88

The first and only reported example of anti-Lu9 (an antibody directed at a low-incidence antigen in the Lutheran blood group system and allelic to the high-incidence antigen Lu6) was described in 1973 in the serum of a white female, Mrs. Mull. Her serum also contained anti-Lu1 (-Lua), and subsequently, an anti-HLA-B7 (-Bga) was identified. We report the second example of anti-Lu9 in a white male (GR), found 25 years later. The GR serum was reactive in the indirect antiglobulin test with Lu:-1,2,6,9 antibody-screening red blood cells (RBCs) using either a low-ionic-saline additive solution or polyethylene glycol for enhancement. Lu:6,9 RBCs were reactive with the serum when ficin- or EDTA/glycine-acid-treated, but nonreactive when trypsin- or a-chymotrypsin-treated. Six known examples of Lu:9 RBCs were reactive with the GR serum. His serum did not contain anti-Lua, anti-HLA-B7 (-Bga) or antibodies to 34 low-incidence antigens tested. We have identified the second example of anti-Lu9 that was likely stimulated by transfusion. Because only one of 200 donors was found to be Lu:9, our study suggests that the incidence of the Lu9 antigen may be less than originally thought.
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PMID:Anti-Lu9: the finding of the second example after 25 years. 1537 13