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Characterization of gp120 hydrolysis by IgA antibodies from humans without HIV infection.

机译:未经HIV感染的人的IgA抗体水解gp120的特性。

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Antibody hydrolysis of the superantigenic gp120 site and HIV-1 neutralization was studied as a potential anti-HIV mechanism in uninfected humans. gp120 hydrolysis by purified serum and salivary antibodies was determined by electrophoresis and peptide sequencing, the proteolytic mechanism was analyzed using electrophilic peptide analogs, and viral neutralization was studied using peripheral blood mononuclear cells as hosts. Polyclonal and monoclonal IgA but not IgG preparations selectively catalyzed the cleavage of HIV gp120 at rates sufficient to predict biologically relevant protection against the virus. The IgA hydrolytic reaction proceeded by noncovalent recognition of gp120 residues 421-433, a component of the superantigenic site of gp120, coordinated with peptide bond cleavage via a serine protease-like mechanism. The Lys-432-Ala-433 bond was one of the cleavage sites. Infection of peripheral blood mononuclear cells by a primary isolate of HIV was neutralized by the IgA but not IgG fractions. The neutralizing activity was specifically inhibited by an electrophilic inhibitor of the catalytic activity. The existence of catalytic IgAs to gp120 in uninfected humans suggests their role in resistance to HIV.
机译:研究了超抗原gp120位点的抗体水解和HIV-1中和作为未感染人类的​​潜在抗HIV机制。通过电泳和肽测序确定纯化的血清和唾液抗体对gp120的水解,使用亲电肽类似物分析蛋白水解机理,并使用外周血单核细胞作为宿主研究病毒中和。多克隆和单克隆IgA而非IgG制剂选择性地催化HIV gp120的裂解,其裂解速率足以预测生物学上对病毒的保护作用。 IgA水解反应通过gp120残基421-433的非共价识别进行,gp120残基是gp120的超抗原性位点,与通过丝氨酸蛋白酶样机制裂解肽键相协调。 Lys-432-Ala-433键是切割位点之一。 IgA可中和HIV的主要分离株对外周血单核细胞的感染,但IgG组分不能。中和活性被催化活性的亲电抑制剂特异性地抑制。在未感染的人类中,存在针对gp120的催化性IgA,表明其对HIV的抵抗力。

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