A simple electronic tool for assessing amino acid sequence polymorphisms within exon-2 of HLA-DPB1 alleles

Abstract

In November 2014, the OPTN/UNOS Board of Directors mandated that HLA-DPB1 typing be performed for all deceased donors. Currently, there are over 1,000 known HLA DPB1 alleles, yet fewer than 30 are represented on commonly used single antigen bead (SAB) solid phase antibody assays. Moreover, the official World Health Organization (WHO) nomenclature for the DPB1 locus does not permit assessment of structural relationships between alleles based on their names. Thus, for donor DPB1 alleles lacking a corresponding SAB, determining the compatibility between a donor-recipient pair when the recipient possesses DPB1 antibodies currently requires the use of manual sequence alignments. Multiple studies have reported that DPB1 alleles can be classified into serological-defined categories based on shared protein sequence motifs residing in distinct hypervariable regions. To date, six such motifs have been recognized. To address this problem, we developed a computer-assisted tool to compare donor and recipient DPB1 allele sequences, specifically those defined by DPB1 hypervariable region motifs located in exon 2 (http://dpreport.hlatools.org). This tool quickly identifies mismatched DPB1 motifs, and easily permits the identification of motif-based donor-specific antibodies (DSA) to DPB1.