Specific amino acid patterns define split specificities of HLA-B15 antigens enabling conversion from DNA-based typing to
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ORIGINAL ARTICLE
Specific amino acid patterns define split specificities of HLA-B15 antigens enabling conversion from DNA-based typing to serological equivalents Burcu Duygu 1,2
&
Benedict M. Matern 1,2 & Lotte Wieten 1,2 & Christina E.M. Voorter 1,2 & Marcel G.J. Tilanus 1,2
Received: 27 April 2020 / Accepted: 10 June 2020 # The Author(s) 2020
Abstract The HLA-B15 typing by serological approaches defined the serological subgroups (or splits) B62, B63, B75, B76, B77 and B70 (B71 and B72). The scarcity of sera with specific anti-HLA antibodies makes the serological typing method difficult to discriminate a high variety of HLA antigens, especially between the B15 antigen subgroups. Advancements in DNA-based technologies have led to a switch from serological typing to high-resolution DNA typing methods. DNA sequencing techniques assign B15 specificity to all alleles in the HLA-B*15 allele group, without distinction of the serological split equivalents. However, the presence of antibodies in the patient defined as split B15 antigens urges the identification of HLA-B*15 allele subtypes of the donor, since the presence of donor-specific antibodies is an important contraindication for organ transplantation. Although the HLA dictionary comprises information regarding the serological subtypes of HLA alleles, there are currently 394 B15 antigens out of 516 in the IPD-IMGT/HLA database (3.38.0) without any assigned serological subtype. In this regard, we aimed to identify specific amino acid patterns for each B*15 serological split, in order to facilitate the assignment of B*15 alleles to serological equivalents after high-resolution molecular typing. As a result, serological specificities of 372/394 not yet assigned alleles could be predicted based on amino acid motifs. Furthermore, two new serological types were identified and added, B62Bw4 and B71-Bw4. Keywords HLA-B*15 amino acid polymorphism . HLA B15 serological equivalents . HLA-B15 splits . LinkSēq™ HLA typing
Introduction Serological typing has been used for a long time to determine HLA typing of patients and donors. This method is based on complement-dependent cytotoxicity (CDC) test or microlymphocytotoxicity assay, which measures the reactivity of a panel of sera containing well-characterized anti-HLA antibodies (Terasaki and McClelland 1964). This Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00251-020-01172-8) contains supplementary material, which is available to authorized users. * Burcu Duygu [email protected] 1
Transplantation Immunology, Tissue Typing Laboratory, Maastricht University Medical Center, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands
2
GROW, School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands
technique has also been performed in the International Histocompatibility Workshops and resulted in the identification of different serological specificities of HLA genes including HLA-B15. In the HLA-B15 antigen group, the serological splits B62,
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