Donor HLA-DQ genetic and functional divergence affect the control of BK polyoma virus infection after kidney transplantation
BK polyomavirus (BKPyV) infection remains a major concern after kidney transplantation, increasing the risk of graft loss in the absence of specific antiviral agent now available. Here, we investigated the impact of HLA diversity on the control of posttransplant BKPyV replication. High HLA evolutionary divergence (HED) at the DQ locus in the donor was an independent predictor of BKPyV-free outcome. More generally, we highlighted the protective effect of highly divergent pairs of HLA-DQ heterodimers corresponding to heterozygous HLA-DQα01/non-DQα01 combinations. We then defined a functional divergence metrics assessed by the similarity of peptide-binding motifs between pairs of HLA-DQ molecules. Greater functional divergence correlated with the size of the BKPyV-derived DQ-bound immunopeptidome and a lower risk of BKPyV reactivation, thus providing a molecular basis for the observed genetic differences. Together, these data provide evidence for a direct link between donor HLA-DQ genetic and functional divergence, diversity of the DQ-bound immunopeptidome, and control of viral infection, likely reflecting stronger antiviral T cell responses.
Authors
- Sophie Caillat‐Zucman (ORCID: https://orcid.org/0000-0002-4535-3550)
- Cyrille Féray
- David Gfeller (ORCID: https://orcid.org/0000-0002-3952-0930)
- Constance Delaugerre (ORCID: https://orcid.org/0000-0001-6081-7993)
- Juliette Villemonteix (ORCID: https://orcid.org/0000-0002-6601-7820)
- Mathieu F. Chevalier (ORCID: https://orcid.org/0000-0002-5601-2217)
- M.N. Peraldi (ORCID: https://orcid.org/0000-0001-9956-3572)
- Jean‐Luc Taupin (ORCID: https://orcid.org/0000-0002-5766-046X)
- Gillian Divard (ORCID: https://orcid.org/0000-0002-3450-0033)
- Jean‐Michel Molina (ORCID: https://orcid.org/0000-0001-8684-2214)
- Julien Racle (ORCID: https://orcid.org/0000-0002-0100-0323)
- Vincent Allain (ORCID: https://orcid.org/0000-0002-1068-7892)
- Linda Feghoul (ORCID: https://orcid.org/0000-0002-2628-7949)
- Julien Gras (ORCID: https://orcid.org/0000-0001-7247-3358)
Institutions
- Université Paris-Sud (FR)
- Inserm (FR)
- Université Paris Cité (FR)
- Saint Louis University Hospital (US)
- Sorbonne Paris Cité (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
- Ludwig Cancer Research (CH)
- Institut Cochin (FR)
- Hôpital Saint-Louis (FR)
- Hôpital Paul-Brousse (FR)
- University of Lausanne (CH)
Publication Details
- Journal
- Science Advances
- Published
- 2025-03-05
- DOI
- https://doi.org/10.1126/sciadv.adt3499
- Citations
- 4
- Primary Topic
- Polyomavirus and related diseases
- Type
- article
- Field-Weighted Citation Impact
- 4.18