IMMUNOGENICITY OF HUMAN PLATELET PROTEINS

产品说明： （摘自申请人摘要）本申请 重点是人体血小板的三维结构 整合素aIIb 3。 库尼基博士提出， 整联蛋白的结构强烈地影响功能和免疫原性。 在GPIIb/IIIa的情况下，存在许多抗原序列 因为它的三级结构。 一个例子是 PlA同种抗原系统。 这些是由多态性创建的， Leu33/Pro33。 然而，这些抗原的表达 在天然异源二聚体中， 全3亚基。 此外，大多数临床相关的自身抗原 与GPIIb/IIIa相关的是“复合物依赖性”。 有些人依赖 在源自每个亚基的非连续序列上，而 一个亚基序列中的其他亚基只有在 亚基与其在功能性受体中的配偶体复合。 GPIIb/IIIa也是一个例子， 蛋白质的抗原性和功能之间的关系。 博士 Kunicki已经鉴定并克隆了GPIIb/IIIa的IgG抑制剂 具有OG独特型的功能。 这些IgG抑制剂还具有 三种特异性蛋白质共有的新识别序列 GPIIb/IIIa的配体，即纤维蛋白原、玻连蛋白和血管内皮素 维勒布兰德因子。 有趣的是，携带OG独特型的抗体 已经进化到拥有识别基序， 可与GPIIb/IIIa结合的相关粘附蛋白。 作为 这些关系的发现继续，我们赞赏， GPIIb/IIIa免疫原性研究是一个稳定的来源， 可转化为GPIIb/IIIa知识的信息 功能

DESCRIPTION: (Adapted from Applicant's Abstract) This application focuses on the three-dimensional structure of the human platelet integrin aIIb3. Dr. Kunicki proposes that the three-dimensional structure of integrins strongly influences function and immunogenicity. In the case of GPIIb/IIIa, many antigenic sequences are present because of its tertiary structure. An example would be the epitopes of the PlA alloantigen system. These are created by a polymorphism, Leu33/Pro33 of the 3 portion. However, expression of such antigens in the native heterodimer is a reflection of the conformation of the entire 3 subunit. Also, most of the clinically-relevant autoantigens associated with GPIIb/IIIa are "complex-dependent". Some depend on non-contiguous sequences originating from each subunit, whereas others in the sequence of one subunit can only be expressed when that subunit is complexed with its partner in a functional receptor. GPIIb/IIIa is also an example between the close relationship between antigenicity and function of the protein. Dr. Kunicki has identified and cloned IgG inhibitors of GPIIb/IIIa function which bear the OG idiotype. These IgG inhibitors also share novel recognition sequences common to three specific protein ligands of GPIIb/IIIa, i.e. fibrinogen, vitronectin and von Willebrand factor. Interestingly, antibodies bearing the OG idiotype have evolved to possess recognition motifs also found in genetically related adhesive proteins which can bind to GPIIb/IIIa. As discovery of these relationships continue, we appreciate that the study of GPIIb/IIIa immunogenicity is a steady source of information that can be translated into knowledge of GPIIb/IIIa function.