Leucine33-proline33 substitution in human platelet glycoprotein IIIa determines HLA-DRw52a (Dw24) association of the immune response against HPA-1a (Zwa/PIA1) and HPA-1b (Zwb/PIA2).
Alloantibody formation against HPA-1a (Zwa/PIA1) has, to date, only been found in HLA-DRw52(a+) (Dw24) individuals. Alloimmunization against the product of the other HPA-1 allele, HPA-1b, is rare. We have been able to evaluate ten cases of HPA-1b alloimmunization in Europe in order to study whether there is an association between HLA phenotype and anti-HPA-1b antibody formation. HLA typing of these patients was performed with particular attention to the DRw52a specificity using specific T-cell clones. No association with DRw52a or any other known HLA phenotype was found. This finding implies that the amino acid substitution leucine33-proline33 in GPIIIa, responsible for HPA-1a/b, is of primary importance for the association of anti-HPA-1a antibody formation with DRw52a. These data show that the amino acid polymorphism affects the presentation of the immunogenic oligopeptides of HPA-1a and -1b in the HLA class-II groove.
Kuijpers
R W
RW
Department of Immunologic Hematology, Central Laboratory of the Netherlands Red Cross Blood Transfusion Serivce, Amsterdam.
von dem Borne
A E
AE
Kiefel
V
V
Eckhardt
C M
CM
Waters
A H
AH
Zupanska
B
B
Barz
D
D
Taaning
E
E
Termijtelen
A
A
Ouwehand
W H
WH
D016824:Antigens, Human Platelet / Q000276:immunology*; D001792:Blood Platelets / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology*; D059810:HLA-DR Serological Subtypes; D006650:Histocompatibility Testing; D006801:Humans; D039661:Integrin beta3; D007518:Isoantibodies / Q000276:immunology; D007930:Leucine / Q000235:genetics / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D010641:Phenotype; D011392:Proline / Q000235:genetics / Q000276:immunology*
D016824:Antigens, Human Platelet; D006684:HLA-DR Antigens; D059810:HLA-DR Serological Subtypes; C051104:HLA-DR52 antigen; C061248:ITGB3 protein, human; D039661:Integrin beta3; D007518:Isoantibodies; D008562:Membrane Glycoproteins; C040580:glycoprotein GP III; D011392:Proline; D007930:Leucine