Molecular characterization of antigenic polymorphisms (Ond(a) and Mart(a)) of the beta(2) family recognized by human leukocyte alloantisera
Molecular characterization of antigenic polymorphisms (Ond(a) and Mart(a)) of the beta(2) family recognized by human leukocyte alloantisera
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DOI：
10.1182/blood.v88.4.1350.bloodjournal8841350
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发表时间：
1996-08-15
期刊：
影响因子：
20.3
通讯作者：
vondemBorne, AEGK
中科院分区：
文献类型：
--
作者：
Simsek, S;vanderSchoot, CE;vondemBorne, AEGK
We show that the previously described alloantisera Ond and Mart, which recognize the alloantigens Ond(a) and Mart(a), react with polymorphic variants of alpha(L) and alpha(M) subunits of the beta(2) integrin family (CD11a and CD11b molecules). This was shown by testing the alloantisera in a monoclonal antibody-specific immobilization of leukocyte antigens, immunoprecipitation, and immunofluorescence assay against cells from normal donors and from patients with leukocyte adhesion deficiency (beta(2) integrin deficient). To elucidate the molecular basis of the Ond(a) and Mart(a) alloantigens, RNA was isolated from mononuclear leukocytes derived from individuals of known serologic phenotype. Reverse transcriptase-polymerase chain reaction (RT-PCR) was performed to amplify the entire coding region of the alpha(L) and alpha(M) mRNAs, The Ond(a) antigen was found to be due to a G2466C substitution in the DNA coding for the alpha(L) subunit, which predicts an Arg766Thr amino-acid polymorphism. The Mart(a) antigen was also found to be due to a single nucleotide substitution (G302A) in the DNA coding for the alpha(M) subunit, which predicts an Arg61His amino acid polymorphism. Using allele-specific restriction enzyme analysis, the association between point mutations and phenotypes was confirmed. The localization of these alloantigens on integrin molecules further illustrates the polymorphic nature of this class of proteins. Whether the polymorphisms influence the adhesive capacity of the leukocyte integrins remains to be investigated. (C) 1996 by The American Society of Hematology.
