A Structurally Based Epitope Analysis of MICA Antibody Specificity Patterns

摘要

Recent studies have suggested a clinical significance to the detection of anti-MICA antibodies in transplantation. We have developed an eplet-based version of the HLAMatchmaker algorithm to assess the epitope specificity of these antibodies. Molecular viewing of the MICA structure and the determination of amino acid sequence differences between MICA alleles has yielded a repertoire of 38 potentially immunogenic MICA eplets. These eplets are based on the functional epitope structure that considers a configuration of amino acids within a three-Ångstrom radius of an antibody-accessible polymorphic residue on the molecular surface.MICA-reactive sera were screened in Luminex assays with single MICA allele panels and analyzed with HLAMatchmaker. We have identified reactivity patterns that correspond to eplet-specific antibodies to identify of unacceptable MICA mismatches including those alleles that have not been tested with the serum.HLAMatchmaker is a useful algorithm to analyze the reactivity patterns of anti-MICA antibodies and the determination of MICA mismatch acceptability at the structural level.