epiArt: a graphical HLA eplet amino acid repertoire translation reveals the need for an epitope driven revision of allele group nomenclature

Abstract

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IntroductionThe immune response after transplantation depends on recipient/donor HLA allele mismatches. To enhance our understanding of the relations of HLA alleles in terms of amino-acid polymorphisms and shared epitopes, we assessed pairwise sequence difference between HLA-alleles.MethodsWe translated amino-acid sequences of confirmed eplets into an atlas of HLA class I and II antigens, followed by visualization of the pairwise allele distances by means of antigen-specific disparity graphs in differential amino-acid space. We obtained an overview of relationships of all alleles of an antigen, corresponding similarity/dissimilarity structures, outliers, alleles with similarity to different antigen groups. Additionally, we calculated prevalence of the amino-acids for each polymorphic sequence position and visualized them in amino-acid motif plots of all alleles belonging to an antigen.ResultsOur visualizations show strongly varying intra-group heterogeneity of HLA class I and II alleles, as well as shared inter-group and inter-locus eplets and epitopes, indicating a benefit of epitope-based transplant matching: Single allele recipient/donor mismatches potentially refer to identical eplets, or to a set of multiple mismatched eplets.DiscussionThis data reveals inconsistencies in the HLA group nomenclature and consequently adds a new level of quality to allocation, motivating the definition of tolerable or taboo mismatches.

Keywords

• HLA alleles
• eplets
• epitopes
• HLA mismatches
• epiart
• confirmed epitopes