Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 8 de 8
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
6.
Nat Biotechnol ; 20(11): 1129-34, 2002 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-12379869

RESUMO

We show that iterative antigen-mediated selection of B-cell lines that constitutively hypermutate their immunoglobulin V genes during culture can be exploited to generate antibodies in vitro. From Ramos, a hypermutating human B-cell line expressing IgM of unknown specificity, we derived descendants that exhibit stepwise improved binding to streptavidin. Binding is initially conferred by mutations in complementarity-determining regions (CDRs), but maturation is due to strategic framework mutations. A more powerful system is provided by a hypermutating chicken B-lymphoma line, owing to its rapid proliferation, high rate of mutation accumulation, and genetic tractability. Starting from a single cell, we selected parallel lineages of derivatives, making mutated antibodies of increasing affinity to independent test antigens. Selection is initiated at an exceedingly low affinity threshold, but antibodies can be delivered with nanomolar affinities. The strategy could prove useful for in vitro generation of antigen-specific monoclonal antibodies and may be extendable to the maturation of other protein-ligand interactions.


Assuntos
Anticorpos Monoclonais/genética , Linfoma de Burkitt/genética , Linfoma de Burkitt/imunologia , Evolução Molecular Direcionada/métodos , Imunoglobulinas Intravenosas/genética , Imunoglobulinas Intravenosas/imunologia , Animais , Anticorpos Monoclonais/biossíntese , Anticorpos Monoclonais/imunologia , Afinidade de Anticorpos/genética , Afinidade de Anticorpos/imunologia , Formação de Anticorpos/efeitos dos fármacos , Formação de Anticorpos/genética , Formação de Anticorpos/imunologia , Sítios de Ligação de Anticorpos/efeitos dos fármacos , Sítios de Ligação de Anticorpos/genética , Linfoma de Burkitt/metabolismo , Galinhas , Clonagem Molecular , Regulação Neoplásica da Expressão Gênica , Humanos , Imunoglobulinas Intravenosas/biossíntese , Mutagênese , Ratos , Valores de Referência , Seleção Genética , Sensibilidade e Especificidade , Especificidade da Espécie , Proteína Estafilocócica A/imunologia , Proteína Estafilocócica A/metabolismo , Estreptavidina/administração & dosagem , Estreptavidina/imunologia , Células Tumorais Cultivadas
7.
Allergy ; 49(2): 69-73, 1994 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-8172361

RESUMO

Substitution therapy with human immunoglobulin preparations is well established in disorders of primary or secondary deficiencies of humoral immunity. However, modifications of the immunoglobulins are required to achieve tolerance for the preferred intravenous route of administration. Several procedures are employed by different commercial suppliers of immunoglobulins, and from the literature it appears that various important biologic functions, e.g., opsonic activity, complement fixation, and Fc-receptor function, are subject to alterations during the preparation. The best preservation of such activity, when assessed in vitro, is obtained with polyethylene glycol precipitation or DEAE-Sephadex fractionation, whereas enzymatic or chemical treatment can potentially reduce the biologic activity. It is recommended that immunoglobulin preparations be evaluated in vitro for intact biologic function before being given to immunodeficient patients.


Assuntos
Imunoglobulinas Intravenosas , Testes de Fixação de Complemento , Humanos , Imunoglobulinas Intravenosas/biossíntese , Imunoglobulinas Intravenosas/imunologia , Imunoglobulinas Intravenosas/metabolismo , Proteínas Opsonizantes , Receptores Fc/metabolismo
8.
Med Dosw Mikrobiol ; 46(4): 349-55, 1994.
Artigo em Polonês | MEDLINE | ID: mdl-7603135

RESUMO

It was shown that all the examined immunoglobulin preparations (IVIG) enhance growth of opsonization of S. aureus, S. epidermidis, E. coli which was studied using the chemiluminescence method. However, no opsonization growth was observed of P. aeruginosa rods with the participation of IVIG (except for Sandoglobulin and the specific immunoglobulin Pseudomonas). We assume that such a result was due to the P. aeruginosa strain's susceptibility to lysis factors of the human serum used in the experiment as the complement source. It was confirmed that phagocytosis with the participation of IVIG measured by the chemiluminescence test requires the presence of a complement. The bactericidal test showed that all IVIG preparations, Pentaglobin in particular, are bactericidal and active against P. aeruginosa. Basing on the results obtained, we believe that the biological activity of the Polish preparation is comparable with the investigated IVIG preparations from foreign firms.


Assuntos
Imunoglobulinas Intravenosas/farmacologia , Fagocitose/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Humanos , Imunoglobulina A/farmacologia , Imunoglobulina M/farmacologia , Imunoglobulinas Intravenosas/biossíntese , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus epidermidis/efeitos dos fármacos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...