Integrin beta-3 (HPA-1a epitope) (ITGB3 (HPA-1a))

Integrin beta-3, also known as CD61 or glycoprotein IIIa, is a critical cell surface receptor on platelets that forms a heterodimer with integrin alpha-IIb to create the GPIIb/IIIa complex (UniProt: P05106). The HPA-1a epitope is a specific antigenic determinant on this protein, defined by a leucine residue at position 33 of the mature protein (PubMed: 29433111). This epitope is the primary target of maternal alloantibodies in Fetal and Neonatal Alloimmune Thrombocytopenia (FNAIT), a condition where a mother lacking the HPA-1a antigen develops antibodies against her fetus's HPA-1a-positive platelets (NIH: StatPearls - Neonatal Alloimmune Thrombocytopenia). These antibodies cross the placenta, leading to fetal platelet destruction and a high risk of intracranial hemorrhage. Therapeutic development focuses on monoclonal antibodies, such as RLYB-212, designed to prevent maternal sensitization by clearing fetal platelets or by blocking the binding of pathogenic maternal antibodies (Rallybio: RLYB-212 Pipeline). Understanding the structural basis of this epitope is essential for developing targeted therapies that do not interfere with the normal hemostatic function of the integrin receptor.

Other names

CD61Platelet glycoprotein IIIaGPIIIaHuman Platelet Antigen 1aZw(a) antigenITGB3 Leu33 variant

Prevention of maternal alloimmunization by rapid clearance of HPA-1a positive fetal platelets from maternal circulation; competitive inhibition of pathogenic maternal alloantibodies.