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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Alloimmunity and Transplantation
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1452637
This article is part of the Research Topic Immunological Aspects Concerning Blood Transfusion View all 3 articles

A Structure-Based in silico Analysis of the Kell Blood Group System

Provisionally accepted
Gabriele Mayr Gabriele Mayr 1Maike Bublitz Maike Bublitz 2*Tim Alexander Steiert Tim Alexander Steiert 1Britt-Sabina Löscher Britt-Sabina Löscher 3Hesham ElAbd Hesham ElAbd 1Michael Wittig Michael Wittig 1Christoph Gassner Christoph Gassner 1,2Andre Franke Andre Franke 1*
  • 1 Institute of Clinical Molecular Biology, Faculty of Medicine, University of Kiel, Kiel, Germany
  • 2 Institute for Translational Medicine, Private University in the Principality of Liechtenstein, Triesen, Liechtenstein
  • 3 Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany

The final, formatted version of the article will be published soon.

    Kell is one of the most complex blood group systems, with a highly polymorphic genetic background. Extensive allelic variations in the KEL gene affect the encoded erythrocyte surface protein Kell. Genetic variants causing aberrant splicing, premature termination of protein translation or specific amino-acid exchanges lead to a variety of different phenotypes with altered Kell expression levels or changes in the antigenic properties of the Kell protein. Using an in silico structural model of the Kell protein, we analyzed the biophysical and structural context of all full-length Kell variants of known phenotype. The results provided insights regarding the 3D co-localization of antigenic Kell variants and led us to suggest several conformational epitopes on the Kell protein surface. We found a number of correlations between the properties of individual genetic variants in the Kell protein and their respective serological phenotypes, which we used as a search filter to predict potentially new immunogenic Kell variants from an in-house whole exome sequencing dataset of 19,772 exomes. Our analysis workflow and results aid blood group serologists in predicting whether a newly identified Kell genetic variant may result in a specific phenotype.

    Keywords: Kell blood group system, Protein structural modeling, KEL missense variants, Antigens, protein variants analysis, phenotype, epitope prediction, antigenicity prediction 31 % and 24% sequence identity with Kell

    Received: 21 Jun 2024; Accepted: 11 Nov 2024.

    Copyright: © 2024 Mayr, Bublitz, Steiert, Löscher, ElAbd, Wittig, Gassner and Franke. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Maike Bublitz, Institute for Translational Medicine, Private University in the Principality of Liechtenstein, Triesen, Liechtenstein
    Andre Franke, Institute of Clinical Molecular Biology, Faculty of Medicine, University of Kiel, Kiel, Germany

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.