Amalia Biron Research Institute of Thrombosis and Hemostasis, Chaim Sheba Medical Center, Tel-Hashomer, Israel.
Transfusion. 2011 Mar;51(3):558-69. doi: 10.1111/j.1537-2995.2010.02862.x. Epub 2010 Aug 30.
Human platelet antigens (HPAs) are polymorphisms in platelet membrane glycoproteins (GPs) that can stimulate production of alloantibodies once exposed to foreign platelets (PLTs) with different HPAs. These antibodies can cause neonatal alloimmune thrombocytopenia, posttransfusion purpura, and PLT transfusion refractoriness. Most HPAs are localized on the main PLT receptors: 1) integrin αIIbβ3, known as the fibrinogen receptor; 2) the GPIb-IX-V complex that functions as the receptor for von Willebrand factor; and 3) integrin α2β1, which functions as the collagen receptor.
We analyzed the structural location and the evolutionary conservation of the residues associated with the HPAs to characterize the features that induce immunologic responses but do not cause inherited diseases.
We found that all HPAs reside in positions located on the protein surface, apart from the ligand-binding site, and are evolutionary variable.
Disease-causing mutations often reside in highly conserved and buried positions. In contrast, the HPAs affect residues on the protein surface that were not conserved throughout evolution; this explains their naive effect on the protein function. Nonetheless, the HPAs involve substitutions of solvent-exposed positions that lead to altered interfaces on the surface of the protein and might present epitopes foreign to the immune system.
人类血小板抗原（HPAs）是血小板膜糖蛋白（GPs）中的多态性，一旦与具有不同 HPAs 的外来血小板（PLT）接触，就会刺激产生同种抗体。这些抗体可导致新生儿同种免疫性血小板减少症、输血后紫癜和 PLT 输注抵抗。大多数 HPAs 定位于主要 PLT 受体上：1）整合素 αIIbβ3，称为纤维蛋白原受体；2）GPIb-IX-V 复合物，作为 von Willebrand 因子的受体；3）整合素 α2β1，作为胶原受体。
我们分析了与 HPAs 相关的残基的结构位置和进化保守性，以表征诱导免疫反应但不引起遗传性疾病的特征。
我们发现所有的 HPAs 都位于蛋白质表面的位置，除了配体结合位点，而且进化上是可变的。
致病突变通常位于高度保守和埋藏的位置。相比之下，HPAs 影响蛋白质表面上未在整个进化过程中保守的残基；这解释了它们对蛋白质功能的先天影响。然而，HPAs 涉及暴露在溶剂中的位置的取代，导致蛋白质表面上的界面改变，并可能呈现免疫系统外的表位。
