Molecular characterization of antigenic polymorphisms (Onda and Marta) of the β2 family recognized by human leukocyte alloantisera

S. Simsek, C. E. Van Der School, M. Daams, E. Huiskes, M. Clay, J. McCullough, C. Van Dalen, D. Stroncek, A. E.G.Kr Von Dem Borne

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Abstract

We show that the previously described alloantisera Ond and Mart, which recognize the alloantigens Onda and Marta, react with polymorphic variants of α(L) and α(M) subunits of the β2 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 (β2 integrin deficient). To elucidate the molecular basis of the Onda and Marta 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 α(L) and α(M) mRNAs. The Onda antigen was found to be due to a G2466C substitution in the DNA coding for the α(L) subunit, which predicts an Arg766Thr amino-acid polymorphism. The Marta antigen was also found to be due to a single nucleotide substitution (G302A) in the DNA coding for the α(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.

Original languageEnglish (US)
Pages (from-to)1350-1358
Number of pages9
JournalBlood
Volume88
Issue number4
DOIs
StatePublished - Aug 15 1996

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