The Human Platelet Alloantigens Bra and Brb Are Associated with a Single Amino Acid Polymorphism on Glycoprotein la ( Integrin Subunit a 2 )
نویسندگان
چکیده
The human GPIa/Ila complex, also known as integrin a2Bfl, serves as a major receptor for collagen in platelets and other cell types. In addition to its role in platelet adhesion to extracellular matrix, GPIa/IIa is also known to bear the clinically important Br' and Br' alloantigenic determinants, which can result in antibody-mediated platelet destruction. Immunochemical studies showed that the Br antigenic epitopes reside solely on the GP Ia subunit and do not depend on sialic acid residues. To define the polymorphism responsible for the Br alloantigen system platelet RNA PCR technique, was used to amplify GPIa mRNA transcripts. Nucleotide sequence analysis of the amplified platelet GPIa cDNA from Bra/a and Brb/b individuals revealed a single A * G polymorphism at base 1648. MnlI RFLP analysis ofcDNA from serologically determined individuals confirmed that this polymorphism segregates with Br phenotype. This single base change results in a substitution of Lys (AAG) in Bra to Glu (GAG) in Brb at amino acid residue 505. In spite of the reversal in charge at this position, however, we found no difference in the ability of Bra and Br' homozygous platelets to adhere to collagens types I, III, or V, nor did antiBra or anti-Br' alloantibodies interfere with platelet adhesion to any of these fibrillar collagens. The identification of the nucleotide substitution that defines the Bra/Brb alloantigen system will now permit both preand postnatal diagnosis for Br phenotype. (J. Clin. Invest. 1993. 92:2427-2432.)
منابع مشابه
The human platelet alloantigens Br(a) and Brb are associated with a single amino acid polymorphism on glycoprotein Ia (integrin subunit alpha 2).
The human GPIa/IIa complex, also known as integrin alpha 2 beta 1, serves as a major receptor for collagen in platelets and other cell types. In addition to its role in platelet adhesion to extracellular matrix, GPIa/IIa is also known to bear the clinically important Br(a) and Brb alloantigenic determinants, which can result in antibody-mediated platelet destruction. Immunochemical studies show...
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