Cloning the antibody response in humans with inflammatory central nervous system disease: analysis of the expressed IgG repertoire in subacute sclerosing panencephalitis brain reveals disease-relevant antibodies that recognize specific measles virus antigens.

Burgoon, M P; Owens, G P; Smith-Jensen, T; Walker, D; Gilden, D H

Burgoon, M P; Owens, G P; Smith-Jensen, T; Walker, D; Gilden, D H.

Afiliación

Burgoon MP; Department of Neurology, University of Colorado Health Sciences Center, Denver 80262, USA.

J Immunol ; 163(6): 3496-502, 1999 Sep 15.

Article en En | MEDLINE | ID: mdl-10477623

RESUMEN

The presence of increased IgG in the brains of humans with infectious and inflammatory CNS diseases of unknown etiology such as multiple sclerosis may be a clue to the cause of disease. For example, the intrathecally synthesized oligoclonal bands (OGBs) in diseases such as subacute sclerosing panencephalitis (SSPE) or cryptococcal meningitis have been shown to represent Ab directed against the causative agents, measles virus (MV) or Cryptococcus neoformans, respectively. Using SSPE as a model system, we have developed a PCR-based strategy to analyze the repertoire of IgG V region sequences expressed in SSPE brain. We observed abnormal expression of germline V segments, overrepresentation of particular sequences that correspond to the oligoclonal bands, and substantial somatic mutation of most clones from the germline, which, taken together, constitute features of Ag-driven selection in the IgG response. Using the most abundant or most highly mutated gamma H chain and kappa or lambda L chain sequences in various combinations, we constructed functional Abs in IgG mammalian expression vectors. Three Abs specifically stained MV-infected cells. One Ab also stained cells transfected with the MV nucleoprotein, and a second Ab stained cells transfected with the MV-fusion protein. This technique demonstrates that functional Abs produced from putative disease-relevant IgG sequences can be used to recognize their corresponding Ags.

Asunto(s)

Anticuerpos Antivirales/biosíntesis; Antígenos Virales/inmunología; Química Encefálica/genética; Química Encefálica/inmunología; Inmunoglobulina G/biosíntesis; Virus del Sarampión/inmunología; Panencefalitis Esclerosante Subaguda/genética; Panencefalitis Esclerosante Subaguda/inmunología; Secuencia de Aminoácidos; Animales; Anticuerpos Antivirales/química; Anticuerpos Antivirales/genética; Antígenos Virales/química; Chlorocebus aethiops; Clonación Molecular; Epítopos/química; Epítopos/inmunología; Humanos; Inmunoglobulina G/química; Inmunoglobulina G/genética; Cadenas Pesadas de Inmunoglobulina/biosíntesis; Cadenas Pesadas de Inmunoglobulina/química; Cadenas Pesadas de Inmunoglobulina/genética; Región Variable de Inmunoglobulina/biosíntesis; Región Variable de Inmunoglobulina/química; Región Variable de Inmunoglobulina/genética; Cadenas kappa de Inmunoglobulina/biosíntesis; Cadenas kappa de Inmunoglobulina/química; Cadenas kappa de Inmunoglobulina/genética; Cadenas lambda de Inmunoglobulina/biosíntesis; Cadenas lambda de Inmunoglobulina/química; Cadenas lambda de Inmunoglobulina/genética; Datos de Secuencia Molecular; Proteínas Recombinantes/biosíntesis; Proteínas Recombinantes/química; Proteínas Recombinantes/genética; Panencefalitis Esclerosante Subaguda/metabolismo; Transfección; Células Vero

Buscar en Google

Añadir a Mi BVS

Imprimir

XML

PubMed Links

Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Panencefalitis Esclerosante Subaguda / Química Encefálica / Inmunoglobulina G / Virus del Sarampión / Anticuerpos Antivirales / Antígenos Virales Tipo de estudio: Prognostic_studies Idioma: En Revista: J Immunol Año: 1999 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

Buscar en Google

Añadir a Mi BVS

Imprimir

XML

PubMed Links