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 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 Br(a/a) and Brb/b individuals revealed a single A<-->G polymorphism at base 1648. MnlI RFLP analysis of cDNA from serologically determined individuals confirmed that this polymorphism segregates with Br phenotype. This single base change results in a substitution of Lys (AAG) in Br(a) 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 Brb homozygous platelets to adhere to collagens types I, III, or V, nor did anti-Bra or anti-Brb 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 pre- and postnatal diagnosis for Br phenotype.
Santoso
S
S
Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen, Germany.
Kalb
R
R
Walka
M
M
Kiefel
V
V
Mueller-Eckhardt
C
C
Newman
P J
PJ
D016824:Antigens, Human Platelet / Q000235:genetics* / Q000276:immunology; D001483:Base Sequence; D001792:Blood Platelets / Q000276:immunology* / Q000502:physiology; D002448:Cell Adhesion / Q000276:immunology; D006801:Humans; D007518:Isoantibodies; D008969:Molecular Sequence Data; D010980:Platelet Membrane Glycoproteins / Q000235:genetics*; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length
C044561:3a alloantigen, human; C071092:5a alloantigen, human; C055973:5b alloantigen, human; D016824:Antigens, Human Platelet; D007518:Isoantibodies; D010980:Platelet Membrane Glycoproteins