No evidence for cross-reactivity of virus-specific antibodies with HLA allo-antigens

Background Antibodies directed against human leucocyte antigens (HLA) can develop through pregnancy, blood transfusions or organ transplants. Anecdotal evidence suggests that virus-specific antibodies may have the capacity to cross-react with HLA, a phenomenon called heterologous immunity, which is well described for T cell alloreactivity. Methods To determine whether antibody cross-reactivity between viral antigens and HLA is common, we tested 51 virus-specific human monoclonal antibodies (mAbs) specific for human immunodeficiency virus (HIV), varicella zoster virus (VZV), cytomegalovirus (CMV), and parvovirus, for reactivity against HLA class I and class II in single antigen bead assays. In addition, we tested the reactivity of 41 HLA-specific human mAbs against common viral antigens of CMV, VZV, HIV, Epstein-Barr virus, and BK polyomavirus. Results No cross-reactivity of any of the virus-specific mAbs with either HLA class I or class II molecules, as well as no cross-reactivity of any of the HLA-specific mAbs with any of the viral antigens was observed. Conclusions These findings indicate that the frequency of cross-reactivity on the antibody level between viral antigens and HLA, if present at all, is low. The emergence of HLA antibodies upon viral infection or vaccination is therefore probably due to bystander activation of dormant HLA-specific memory B cells. *Corresponding author: Dr. Sebastiaan Heidt, Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Albinusdreef 2 - 2333 ZA Leiden, the Netherlands. e-mail: S.Heidt@lumc.nl Conflict of interest: The authors have declared that no conflict of interest exists. Funding: None Authorship Sebastiaan Heidt: designed study, interpreted results, wrote manuscript Mariet C. Feltkamp: designed study, edited manuscript Gonca E Karahan: performed experiments, interpreted results Caroline S. de Brouwer: performed experiments, interpreted results Janneke Langerak-Langerak: performed experiments Arend Mulder: designed study, edited manuscript Frans HJ Claas: designed study, edited manuscript Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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