HUMAN PLATELET ANTIGEN-3 (HPA-3) - LOCALIZATION OF THE DETERMINANT OFTHE ALLOANTIBODY LEK(A) (HPA-3A) TO THE C-TERMINUS OF PLATELET GLYCOPROTEIN IIB HEAVY-CHAIN AND CONTRIBUTION OF O-LINKED CARBOHYDRATES

The human platelet antigen (HPA) 3 system is expressed on GPIIb, one s ubunit of GPIIb-IIIa, the platelet fibrinogen receptor. It was recentl y shown that HPA-3 was associated with an Ile843/Ser polymorphism. To investigate further HPA-3 determinant structure, we localized an HPA-3 a determinant, recognized by the alloantiserum Lek(a), within the last 29 amino acids of GPIIbalpha. This region encompasses the polymorphic Ile843, which, as expected, is substituted into Ser in Lek(a)-negativ e individuals, as shown by DNA sequence after polymerase chain reactio n on platelet RNA. In addition, contribution of glycosylation to the d eterminant structure was demonstrated since the Lek(a) antigenicity wa s strongly decreased after specifically removing non-terminal O-linked sugars, but not terminal sialic acids. We have thus refined the local ization of an HPA-3a determinant within the last 29 amino acids, inclu ding Ile843, of GPIIb heavy chain, and shown that the Lek(a) HPA-3a de terminant is dependent, in part, upon the serine-linked carbohydrates adjacent to Ile/Ser843.