scholarly journals Molecular composition of an antigen-specific, Ly-1 T suppressor inducer factor. One molecule binds antigen and is I-J-; another is I-J+, does not bind antigen, and imparts an Igh-variable region-linked restriction.

1982 ◽  
Vol 155 (3) ◽  
pp. 655-665 ◽  
Author(s):  
K Yamauchi ◽  
N Chao ◽  
D B Murphy ◽  
R K Gershon

Immunized Ly-1+2-T cells (Ly-1 cells) make an antigen-specific soluble suppressor product (Lyl-1 TsiF) that will induce Ly-2+ cells to express suppressive activity but only if the Ly-2+ and the Ly-1 producer cell share genetic polymorphisms that are linked to the Igh locus and in particular that part where the Igh-V (or VH) is encoded. Ly-1 TsiF can be separated into entities, one binds antigen and does not express I-J determinants, and the other is I-J+ and does not bind antigen. Neither of these "subfactors" has biological activity, but a 50:50 mixture of them reconstitutes biological activity that expresses the antigen specificity of the antigen-binding molecule. Any of the three heterologous erythrocytes (antigens) studied can be used for immunization to produce the I-J+ nonantigen-binding factor, i.e., the I-J+ moiety makes no contribution to the factor's specificity. It does, however, determine the intact factor's Igh-V linked restriction. Thus, the antigen combining site of the factor is irrelevant to the factor's Igh-V restriction but crucial for its specificity. The I-J+ molecule does not bind antigen nor influence the factor's antigen specificity but expresses the Igh-V polymorphism (or anti-Igh-V polymorphism) that is required for the transmission of an inductive signal to the factor's Ly-2+ acceptor cell.

1983 ◽  
Vol 158 (6) ◽  
pp. 1938-1947 ◽  
Author(s):  
P M Flood ◽  
A Lowy ◽  
A Tominaga ◽  
B Chue ◽  
M I Greene ◽  
...  

Immunized Ly-1 T cells secrete an antigen-specific molecule that will induce Ly-2+ T cells to express suppressive activity. In two separate systems, factors that suppress the primary anti-sheep erythrocyte (SE) plaque-forming cell response of spleen cells in vitro (Ly-1 TsiF) or the contact sensitivity of azobenzenearsonate (ABA)-TsF1 consist of two macromolecules, one which binds antigen and is IJ-, the other which is I-J+ and does not bind antigen. Both of these chains are required for the factor's biological activity. These factors show a genetic restriction in their ability to induce suppression that is linked to the variable region of the Ig heavy chain gene complex (Igh-V). The I-J+ chain from the ABA-specific TsF1 could replace the I-J+ chain needed by the SE-specific Ly-1 TsiF for biological activity. Mixtures of ABA-binding chain with I-J+ material obtained from the SE-specific Ly-1 TsiF had no effect on the primary anti-SE response in vitro. In mixtures of SE antigen-binding chain from Ly-1 TsiF and I-J+ material from the ABA-specific TsF1, it is the I-J+ molecule that determined the factor's Igh-V restriction. Thus, the antigen-combining site of the factor determined the antigen specificity of this factor but is irrelevant to its Igh-V-linked genetic restrictions. The implications of these results for the idiotype network hypothesis are discussed.


2020 ◽  
Vol 7 ◽  
Author(s):  
Monica L. Fernández-Quintero ◽  
Katharina B. Kroell ◽  
Martin C. Heiss ◽  
Johannes R. Loeffler ◽  
Patrick K. Quoika ◽  
...  

Fab consist of a heavy and light chain and can be subdivided into a variable (VH and VL) and a constant region (CH1 and CL). The variable region contains the complementarity-determining region (CDR), which is formed by six hypervariable loops, shaping the antigen binding site, the paratope. Apart from the CDR loops, both the elbow angle and the relative interdomain orientations of the VH–VL and the CH1–CL domains influence the shape of the paratope. Thus, characterization of the interface and elbow angle dynamics is essential to antigen specificity. We studied nine antigen-binding fragments (Fab) to investigate the influence of affinity maturation, antibody humanization, and different light-chain types on the interface and elbow angle dynamics. While the CDR loops reveal conformational transitions in the micro-to-millisecond timescale, both the interface and elbow angle dynamics occur on the low nanosecond timescale. Upon affinity maturation, we observe a substantial rigidification of the VH and VL interdomain and elbow-angle flexibility, reflected in a narrower and more distinct distribution. Antibody humanization describes the process of grafting non-human CDR loops onto a representative human framework. As the antibody framework changes upon humanization, we investigated if both the interface and the elbow angle distributions are changed or shifted. The results clearly showed a substantial shift in the relative VH–VL distributions upon antibody humanization, indicating that different frameworks favor distinct interface orientations. Additionally, the interface and elbow angle dynamics of five antibody fragments with different light-chain types are included, because of their strong differences in elbow angles. For these five examples, we clearly see a high variability and flexibility in both interface and elbow angle dynamics, highlighting the fact that Fab interface orientations and elbow angles interconvert between each other in the low nanosecond timescale. Understanding how the relative interdomain orientations and the elbow angle influence antigen specificity, affinity, and stability has broad implications in the field of antibody modeling and engineering.


2015 ◽  
Vol 112 (6) ◽  
pp. 1815-1820 ◽  
Author(s):  
Sherry G. Lin ◽  
Chunguang Guo ◽  
Arthur Su ◽  
Yu Zhang ◽  
Frederick W. Alt

Ig heavy chain (IgH) variable region exons are assembled from V, D, and J gene segments during early B-lymphocyte differentiation. A several megabase region at the “distal” end of the mouse IgH locus (Igh) contains hundreds of VHs, separated by an intergenic region from Igh Ds, JHs, and constant region exons. Diverse primary Igh repertoires are generated by joining Vs, Ds, and Js in different combinations, with a given B cell productively assembling only one combination. The intergenic control region 1 (IGCR1) in the VH-to-D intergenic region regulates Igh V(D)J recombination in the contexts of developmental order, lineage specificity, and feedback from productive rearrangements. IGCR1 also diversifies IgH repertoires by balancing proximal and distal VH use. IGCR1 functions in all these regulatory contexts by suppressing predominant rearrangement of D-proximal VHs. Such IGCR1 functions were neutralized by simultaneous mutation of two CCCTC-binding factor (CTCF)-binding elements (CBE1 and CBE2) within it. However, it was unknown whether only one CBE mediates IGCR1 functions or whether both function in this context. To address these questions, we generated mice in which either IGCR1 CBE1 or CBE2 was replaced with scrambled sequences that do not bind CTCF. We found that inactivation of CBE1 or CBE2 individually led to only partial impairment of various IGCR1 functions relative to the far greater effects of inactivating both binding elements simultaneously, demonstrating that they function cooperatively to achieve full IGCR1 regulatory activity. Based on these and other findings, we propose an orientation-specific looping model for synergistic CBE1 and CBE2 functions.


2015 ◽  
Vol 12 (1) ◽  
pp. 3910-3918 ◽  
Author(s):  
Dr Remon M Zaki ◽  
Prof Adel M. Kamal El-Dean ◽  
Dr Nermin A Marzouk ◽  
Prof Jehan A Micky ◽  
Mrs Rasha H Ahmed

 Incorporating selenium metal bonded to the pyridine nucleus was achieved by the reaction of selenium metal with 2-chloropyridine carbonitrile 1 in the presence of sodium borohydride as reducing agent. The resulting non isolated selanyl sodium salt was subjected to react with various α-halogenated carbonyl compounds to afford the selenyl pyridine derivatives 3a-f  which compounds 3a-d underwent Thorpe-Ziegler cyclization to give 1-amino-2-substitutedselenolo[2,3-b]pyridine compounds 4a-d, while the other compounds 3e,f failed to be cyclized. Basic hydrolysis of amino selenolo[2,3-b]pyridine carboxylate 4a followed by decarboxylation furnished the corresponding amino selenolopyridine compound 6 which was used as a versatile precursor for synthesis of other heterocyclic compound 7-16. All the newly synthesized compounds were established by elemental and spectral analysis (IR, 1H NMR) in addition to mass spectra for some of them hoping these compounds afforded high biological activity.


HortScience ◽  
1998 ◽  
Vol 33 (3) ◽  
pp. 557d-557
Author(s):  
Jennifer Warr ◽  
Fenny Dane ◽  
Bob Ebel

C6 volatile compounds are known to be produced by the plant upon pathogen attack or other stress-related events. The biological activity of many of these substances is poorly understood, but some might produce signal molecules important in host–pathogen interactions. In this research we explored the possibility that lipid-derived C6 volatiles have a direct effect on bacterial plant pathogens. To this purpose we used a unique tool, a bacterium genetically engineered to bioluminesce. Light-producing genes from a fish-associated bacterium were introduced into Xanthomonas campestris pv. campestris, enabling nondestructive detection of bacteria in vitro and in the plant with special computer-assisted camera equipment. The effects of different C6 volatiles (trans-2 hexanal, trans-2 hexen-1-ol and cis-3 hexenol) on growth of bioluminescent Xanthomonas campestris were investigated. Different volatile concentrations were used. Treatment with trans-2 hexanal appeared bactericidal at low concentrations (1% and 10%), while treatments with the other volatiles were not inhibitive to bacterial growth. The implications of these results with respect to practical use of trans-2 hexanal in pathogen susceptible and resistant plants will be discussed.


2015 ◽  
Vol 4 (2) ◽  
pp. 205
Author(s):  
Indarto Indarto

Artocarpus plant  dadah  Miq.  is one of the species of Artocarpus of the Moraceae family that belongs to a rare plant in nature. This plant is known as the main source of phenolic derivative compound that is flavone compound  in  or  tri-oxygenated and terisoprenilasi in C-3 position ,  and also known as the main source of phenolic compound derived flavonoids, aryl-benzofuran, stilbenoid and xanthane flavonoida, which have biological activity as promoters antitumor, antibacterial, antifungal, antiimflamatori, antikanker and others. This study aimed to isolate and identify the phenolic compounds contained in plant  A .  dadah obtained from the village of Purwoasri, North Metro District, Metro City, Lampung Province. Research stages include collection and sample preparation and extraction, isolation, and purification of compounds using KCV method, flash chromatography  , KKG, and TLC, while the identification of compounds is performed using ultraviolet-visible (UV-VIS) and infrared (IR) spectroscopy. In the present study, three compounds were isolated, one of which was estimated to be flavonoid compounds based on UV-VIS and IR spectra data which also had high activity against murine leukemia P-388 cells with IC 50  3.1 μg / mL. Based on the IR spectral data for the other two compounds there is a -OH uptake in the region of 3200-3500 cm -1, C = C aromatic uptake in the area of 1600-1400 cm -1 , so it is estimated that both compounds are phenolic group compounds.Tumbuhan Artocarpus dadah Miq.merupakan salah satu spesies Artocarpus dari famili Moraceae yang termasuk tumbuhan langka di alam. Tumbuhan ini dikenal sebagai sumber utama senyawa turunan fenolik yaitu senyawa flavon di atau tri-oksigenasi dan terisoprenilasi pada posisi C-3, dan juga dikenal sebagai sumber utama senyawa fenolik turunan flavonoid, aril-benzofuran, stilbenoid dan santon turunan flavonoida, yang memiliki aktivitas biologi sebagai promotor antitumor, antibakteri, antifungal, antiimflamatori, antikanker dan lain-lain.Penelitian ini bertujuan untuk mengisolasi dan mengidentifikasi senyawa fenolik yang terkandung dalam tumbuhan A. dadah yang diperoleh dari desa Purwoasri, Kecamatan Metro Utara, Kota Metro, Provinsi Lampung.Tahapan penelitian yang dilakukan meliputi pengumpulan dan persiapan sampel kemudian ekstraksi, isolasi, dan pemurnian senyawa menggunakan metode KCV, kromatografi flash, KKG, dan KLT, sedangkan identifikasi senyawa dilakukan menggunakan spektroskopi ultraungu-tampak (UV-VIS) dan inframerah (IR). Pada penelitian ini telah berhasil diisolasi tiga senyawa, yang salah satunya diperkirakan senyawa flavonoid berdasarkan data spektrum UV-VIS dan IR yang juga memiliki aktivitas tinggi terhadap sel murine leukemia P-388 dengan IC50 3,1 μg/mL. Berdasarkan data spektrum IR untuk dua senyawa yang lain terdapat serapan –OH pada daerah 3200-3500 cm-1, serapan C=C aromatik di daerah 1600-1400 cm-1, sehingga diperkirakan kedua senyawa tersebut merupakan senyawa golongan fenolik.


1982 ◽  
Vol 156 (3) ◽  
pp. 924-929 ◽  
Author(s):  
D Primi ◽  
F Mami ◽  
C Le Guern ◽  
P A Cazenave

On the basis of previous frequency determinations we could set up large numbers of cultures, each containing less than one competent precursor B cell specific for beta-galactosidase or for each of three idiotopes previously found on a monoclonal anti-beta-galactosidase antibody. Cultures were polyclonally activated by either lipopolysaccharide or Nocardia-delipidated cell mitogen. Each culture supernatant was individually tested for hemagglutination activity against sheep erythrocytes coupled with beta-galactosidase or with each of the three purified monoclonal anti-idiotypic antibodies. The results showed that only a minority of those clones positive for only one or two idiotopes recognized antigen. However, all those clones simultaneously positive for the three V region determinants recognized beta-galactosidase. The implications of these results for our understanding of the relationship between the antigen-binding site and idiotope expression are discussed.


1964 ◽  
Vol 2 (6) ◽  
pp. 21-22

L-thyroxine (Eltroxin - Glaxo; and others), liothyronine (Tertroxin - Glaxo; and others), a mixture of l-thyroxine and l-triiodothyronine (Diotroxin - Glaxo) and dried thyroid (Thyroid BP) are all used in the management of hypothyroidism. Large quantities of Thyroid BP are unfortunately still prescribed, probably not all for the treatment of demonstrable hypothyroidism. Unlike the other preparations, it is not a pure substance and needs to be assayed biologically. Chemical assay which is required by the British Pharmacopoeia does not reflect comparable biological activity.


1981 ◽  
Vol 153 (5) ◽  
pp. 1246-1259 ◽  
Author(s):  
M Fresno ◽  
G Nabel ◽  
L McVay-Boudreau ◽  
H Furthmayer ◽  
H Cantor

We have generated continuously propagatable T lymphocyte clones to study antigen-specific T cell functions. All Ly-2+ clones mediate suppressive activity and secrete a characteristic pattern of polypeptides that differs from Ly-2- T cell clones. Cells of one clone, Cl.Ly23/4, specifically bind glycophorin from sheep erythrocytes (SRBC). After incubation with [35S]methionine, supernate material from this clone also contains biosynthetically labeled 70,000-mol wt proteins that specifically bind to SRBC and this binding is inhibited by glycophorin from sheep but not other erythrocytes. These antigen-binding 70,000-mol wt peptides specifically and completely suppress primary anti-SRBC responses generated by mixtures of primed Ly-1+2- cells and B cells. Suppression by these antigen-binding peptides reflects direct inhibition of T-helper activity.


Antioxidants ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 340
Author(s):  
Sara Hurtado-Barroso ◽  
Paola Quifer-Rada ◽  
María Marhuenda-Muñoz ◽  
Jose Fernando Rinaldi de Alvarenga ◽  
Anna Tresserra-Rimbau ◽  
...  

Consumption of organic products is increasing yearly due to perceived health-promoting qualities. Several studies have shown higher amounts of phytochemicals such as polyphenols and carotenoids in foods produced by this type of agriculture than in conventional foods, but whether this increase has an impact on humans still needs to be assessed. A randomized, controlled and crossover study was carried out in nineteen healthy subjects aged 18–40 years, who all followed an organic and conventional healthy diet, both for a 4-week period. Analysis of biological samples revealed a significant increase on the excretion of 4-hydroxybenzoic acid (4-HBA), a phenolic metabolite with biological activity, after the organic intervention. However, no changes were observed in the other variables analyzed.


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