Human Platelet Antigen 3 (HPA-3): Localization of the Determinant of the Alloantibody Lek^a (HPA-3a) to the C-Terminus of Platelet Glycoprotein IIb Heavy Chain and Contribution of O-Linked Carbohydrates

Summary

The human platelet antigen (HPA) 3 system is expressed on GPIIb, one subunit of GPIIb-IIIa, the platelet fibrinogen receptor. It was recently shown that HPA-3 was associated with an Ile₈₄₃/Ser polymorphism. To investigate further HPA-3 determinant structure, we localized an HPA-3a determinant, recognized by the alloantiserum Lek^a, within the last 29 amino acids of GPIIbα. This region encompasses the polymorphic Ile₈₄₃, which, as expected, is substituted into Ser in Lek^a-negative individuals, as shown by DNA sequence after polymerase chain reaction on platelet RNA. In addition, contribution of glycosylation to the determinant structure was demonstrated since the Lek^a antigenicity was strongly decreased after specifically removing nonterminal O-linked sugars, but not terminal sialic acids. We have thus refined the localization of an HPA-3a determinant within the last 29 amino acids, including Ile₈₄₃, of GPIIb heavy chain, and shown that the Lek^a HPA-3a determinant is dependent, in part, upon the serine-linked carbohydrates adjacent to Ile/Ser₈₄₃.

• References

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