Fc-dependent and Fc-independent opsonization of Cryptococcus neoformans by anticapsular monoclonal antibodies: importance of epitope specificity.
Fc-dependent and Fc-independent opsonization of Cryptococcus neoformans by anticapsular monoclonal antibodies: importance of epitope specificity.
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抗荚膜单克隆抗体对新型隐球菌的 Fc 依赖性和 Fc 非依赖性调理作用：表位特异性的重要性。
DOI：
10.1128/iai.70.6.2812-2819.2002
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发表时间：
2002
影响因子：
3.1
通讯作者：
Kozel,ThomasR
中科院分区：
文献类型：
--
作者：
Netski,Dale;Kozel,ThomasR
葡萄糖醛酸甘露聚糖（GXM），主要的荚膜多糖酵母新生隐球菌反应的单克隆抗体（MAbs），产生不同的荚膜反应时，观察微分干涉相差显微镜。这些反应取决于抗体的表位特异性。检查了产生称为边缘和肿胀模式的免疫球蛋白G1（IgG1）单克隆抗体的调理素活性。边缘模式MAb与GXM血清型A、B、C和D共有的表位反应。蓬松型单克隆抗体仅与血清型A和D反应。在吞噬试验中，使用血清型A细胞和居民小鼠腹腔巨噬细胞，边缘模式单克隆抗体明显比蓬松模式单克隆抗体更调理。F（ab′）2片段与正常人血清中的热不稳定因子对酵母的调理作用具有协同作用。与正常血清相比，虚胖型单克隆抗体的F（ab′）2片段在调理作用上也有协同作用，但其水平远低于边缘型单克隆抗体。单独的正常血清不是调理剂。在无血清条件下，F（ab′）2片段的边缘型单克隆抗体（而非蓬松型单克隆抗体）可刺激被包裹隐球菌的吞噬作用。用纯化的GXM预处理巨噬细胞可消除F（ab′）2片段的这种非血清依赖性调理作用，表明吞噬细胞GXM受体参与其中。结果表明：（i）抗荚膜IgG单克隆抗体通过多种机制促进对包囊隐球菌的吞噬作用，（ii）一些抗GXM抗体以Fc非依赖性方式具有调理作用，（iii）调理活性与荚膜反应相关，并以表位特异性方式发生。
Monoclonal antibodies (MAbs) reactive with glucuronoxylomannan (GXM), the major capsular polysaccharide of the yeastCryptococcus neoformans, produce distinct capsular reactions when viewed by differential interference contrast microscopy. These reactions depend on the epitope specificity of the antibody. Opsonic activities of immunoglobulin G1 (IgG1) MAbs that produce patterns termed rim and puffy were examined. Rim-pattern MAbs are reactive with an epitope shared by GXM serotypes A, B, C, and D. Puffy-pattern MAbs are reactive only with serotypes A and D. In phagocytosis assays, using serotype A cells and resident murine peritoneal macrophages, rim-pattern MAbs were markedly more opsonic than puffy-pattern MAbs. F(ab′)2fragments of rim-pattern MAbs were synergistic with heat-labile factors in normal human serum for opsonization of the yeast. F(ab′)2fragments of puffy-pattern MAbs were also synergistic with normal serum in opsonization but at a much lower level than fragments of rim-pattern MAbs. Normal serum alone was not opsonic. F(ab′)2fragments of rim-pattern MAbs, but not puffy-pattern MAbs, stimulated phagocytosis of encapsulated cryptococci in the absence of serum. This serum-independent opsonic action of F(ab′)2fragments was abrogated by pretreatment of macrophages with purified GXM, suggesting the involvement of a phagocyte GXM receptor. The results indicate that (i) there are multiple mechanisms by which anticapsular IgG MAbs facilitate phagocytosis of encapsulated cryptococci, (ii) some anti-GXM antibodies are opsonic in an Fc-independent manner, and (iii) opsonic activity correlates with the capsular reaction and occurs in an epitope-specific manner.