Polymorphisms of MICA recognized by human alloantibodies

Yizhou Zou, Zhiqiang Qin, Allison Silveus, Yisun Fan, Peter Stastny

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

MICA antigens are polymorphic glycoproteins expressed on the surface of human endothelial cells and other cells. Antibodies against MICA have been found in transplant recipients and were found to be associated with decreased survival of kidney allografts. In the present work, we investigated the polymorphisms that are recognized by antibodies against MICA. Soluble MICA recombinant proteins representing 11 common alleles, two hybrid alleles, and two single amino acid mutated alleles were produced. Patterns of reactivity were determined with MICA bound to Luminex beads. In some studies, sera containing antibodies against MICA were absorbed by cell lines transfected with MICA*001, MICA*002, MICA*008, and MICA*009 or with untransfected cells, followed by testing of antibody reactivity against MICA proteins bound to beads. The monoclonal antibodies and sera used in this study were found to recognize up to 14 distinct MICA epitopes as demonstrated by their differential absorption/reactivity patterns. Among these, nine epitopes correlated with a single unique amino acid: one shared two signature amino acids, one shared three signature amino acids in close proximity, and three epitopes involved multiple amino acids in a nonlinear sequence. Two groups of public epitopes (MICA-G1 and MICA-G2) were characterized. MICA shared epitopes were determined by reactivity loss in single MICA antigen bead assays by absorption with MICA transfectants. Since these epitopes may be targets for antibody binding and possibly antibody-mediated allograft rejection, epitope identification may help understand the development of MICA antibodies and to identify suitable donors for sensitized transplant recipients.

Original languageEnglish (US)
Pages (from-to)91-100
Number of pages10
JournalImmunogenetics
Volume61
Issue number2
DOIs
StatePublished - Feb 1 2009

Keywords

  • Alloantibodies
  • Epitope
  • MHC class I related gene A (MICA)

ASJC Scopus subject areas

  • Immunology
  • Genetics

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    Zou, Y., Qin, Z., Silveus, A., Fan, Y., & Stastny, P. (2009). Polymorphisms of MICA recognized by human alloantibodies. Immunogenetics, 61(2), 91-100. https://doi.org/10.1007/s00251-008-0344-9