HLA graph, a free and ready‐to‐use bioinformatics tool to explore anti‐HLA eplets reactivity pattern

Abstract

Introduction HLA antigens are highly polymorphic, and their immunogenicity is dependent on the configurations of polymorphic amino acids. Monitoring anti‐HLA immunization is essential in organ transplantation, as antibodies directed against HLA molecules are a major cause of rejection. Anti‐HLA antibodies are not specific for HLA antigens, but recognize B‐cell epitopes present on HLA molecules. Methods To better understand antibody reactivity patterns, we calculated the Spearman correlation of the mean fluorescence intensity (MFI) of anti‐HLA antibodies identified by a single‐antigen assay performed using a Luminex® immunobeads assay on a large number of samples. Then, we built a computer tool analyzing antibody reactivity patterns with an accessibility by a web browser linked to the International Epitope Registry. We also extended our model to Onelambda® and Lifecodes® single‐antigen class I and class II assays. Results and Discussion The resulting MFI correlations reflect HLA antibody cross‐reactivity and eplets similarity. We built HLA Graph, a computer tool that analyzes the eplets involved in antibody reactivity profiles. HLA Graph is usable with Onelambda® and Lifecodes® single‐antigen class I and class II assays. The interpretation of reactivity against alleles not tested by the antibody assays and against the alpha and beta chains of HLA‐DQ and HLA‐DP loci were also developed. Conclusion HLA Graph is a free and ready‐to‐use bioinformatics tool that can be used by all laboratories performing anti‐HLA antibody identification by immunobead assay.

First Impressions Matter: Immune Imprinting and Antibody Cross-Reactivity in Influenza and SARS-CoV-2

“…Such information has been used to predict antibody reactivity in solid organ transplantation by knowing donor HLA molecular typing and recipient anti-HLA antibody specificities, a process called a virtual cross-match [ 70 ]. This prediction allows shortening the time to clear an organ donor-recipient pair for an organ transplant and allows prediction of how the development of anti-HLA antibodies will influence the percentage of organ donors by antibody specificity and HLA eplets [ 71 , 72 , 73 ]. Thus, similarly identifying and characterizing eplets on viral surface proteins may provide a more accurate method of characterizing antibody mediated B cell immunity to viral pathogens, and aiding in vaccine design.…”

Platelet transfusions in haploidentical haematopoietic stem cell allograft candidates: Protecting HLA‐A and HLA‐B antigens through eplet analysis

“…Specific polymorphic regions in HLA molecules determine the nature of public epitopes (encoded by many different HLA alleles) and private epitopes (encoded by very few other HLA allele products). 7,8 Many public epitopes have been structurally defined. By way of an example, the Bw4/Bw6 public epitopes differentiate between two HLA-B antigen profiles and are also shared by a few HLA-A molecules.…”

“…Hence, matching on the epitope level might be more relevant for avoiding anti‐HLA class I immunization with haploidentical donors. Specific polymorphic regions in HLA molecules determine the nature of public epitopes (encoded by many different HLA alleles) and private epitopes (encoded by very few other HLA allele products) 7,8 . Many public epitopes have been structurally defined.…”