HLA-DQ-Specific Recombinant Human Monoclonal Antibodies Allow for In-Depth Analysis of HLA-DQ Epitopes

Suzanne Bezstarosti, Cynthia S.M. Kramer, Marry E.I. Franke-van Dijk, Manon Vergunst, Kim H. Bakker, Merve Uyar-Mercankaya, Rico Buchli, Dave L. Roelen, Johan W. de Fijter, Frans H.J. Claas, Sebastiaan Heidt*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

11 Citations (Scopus)

Abstract

HLA-DQ donor-specific antibodies (DSA) are the most prevalent type of DSA after renal transplantation and have been associated with eplet mismatches between donor and recipient HLA. Eplets are theoretically defined configurations of surface exposed amino acids on HLA molecules that require verification to confirm that they can be recognized by alloantibodies and are therefore clinically relevant. In this study, we isolated HLA-DQ specific memory B cells from immunized individuals by using biotinylated HLA-DQ monomers to generate 15 recombinant human HLA-DQ specific monoclonal antibodies (mAb) with six distinct specificities. Single antigen bead reactivity patterns were analyzed with HLA-EMMA to identify amino acids that were uniquely shared by the reactive HLA alleles to define functional epitopes which were mapped to known eplets. The HLA-DQB1*03:01-specific mAb LB_DQB0301_A and the HLA-DQB1*03-specific mAb LB_DQB0303_C supported the antibody-verification of eplets 45EV and 55PP respectively, while mAbs LB_DQB0402_A and LB_DQB0602_B verified eplet 55R on HLA-DQB1*04/05/06. For three mAbs, multiple uniquely shared amino acid configurations were identified, warranting further studies to define the inducing functional epitope and corresponding eplet. Our unique set of HLA-DQ specific mAbs will be further expanded and will facilitate the in-depth analysis of HLA-DQ epitopes, which is relevant for further studies of HLA-DQ alloantibody pathogenicity in transplantation.

Original languageEnglish
Article number761893
JournalFrontiers in Immunology
Volume12
DOIs
Publication statusPublished - 7 Jan 2022
Externally publishedYes

Bibliographical note

Publisher Copyright:
Copyright © 2022 Bezstarosti, Kramer, Franke-van Dijk, Vergunst, Bakker, Uyar-Mercankaya, Buchli, Roelen, de Fijter, Claas and Heidt.

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