HLA class I peptide polymorphisms contribute to class II DQβ0603:DQα0103 antibody specificity.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
19 Jan 2024
Historique:
received: 14 07 2023
accepted: 03 01 2024
medline: 20 1 2024
pubmed: 20 1 2024
entrez: 19 1 2024
Statut: epublish

Résumé

Antibodies reactive to human leukocyte antigens (HLA) represent a barrier for patients awaiting transplantation. Based on reactivity patterns in single-antigen bead (SAB) assays, various epitope matching algorithms have been proposed to improve transplant outcomes. However, some antibody reactivities cannot be explained by amino acid motifs, leading to uncertainty about their clinical relevance. Antibodies against the HLA class II molecule, DQβ0603:DQα0103, present in some candidates, represent one such example. Here, we show that peptides derived from amino acids 119-148 of the HLA class I heavy chain are bound to DQβ0603:DQα0103 proteins and contribute to antibody reactivity through an HLA-DM-dependent process. Moreover, antibody reactivity is impacted by the specific amino acid sequence presented. In summary, we demonstrate that polymorphic HLA class I peptides, bound to HLA class II proteins, can directly or indirectly be part of the antibody binding epitope. Our findings have potential important implications for the field of transplant immunology and for our understanding of adaptive immunity.

Identifiants

pubmed: 38242876
doi: 10.1038/s41467-024-44912-0
pii: 10.1038/s41467-024-44912-0
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

609

Informations de copyright

© 2024. The Author(s).

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Auteurs

N Remi Shih (NR)

Terasaki Innovation Center, Los Angeles, CA, USA.

Thoa Nong (T)

Terasaki Innovation Center, Los Angeles, CA, USA.

Cathi Murphey (C)

Southwest Immunodiagnostics, Inc., San Antonio, TX, USA.

Mayra Lopez-Cepero (M)

Terasaki Innovation Center, Los Angeles, CA, USA.

Peter W Nickerson (PW)

Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada.

Jean-Luc Taupin (JL)

Laboratoire d'Immunologie et Histocompatibilité and INSERM U976 IRSL, Hôpital Saint-Louis APHP, Paris, France.

Magali Devriese (M)

Laboratoire d'Immunologie et Histocompatibilité and INSERM U976 IRSL, Hôpital Saint-Louis APHP, Paris, France.

Jakob Nilsson (J)

Department of Immunology, University Hospital Zurich, Zurich, Switzerland.

Marie-Benedicte Matignon (MB)

Department of Nephrology and Transplantation, Hôpital Henri Mondor APHP, Creteil, France.

Robert A Bray (RA)

Department of Pathology, Emory University, Atlanta, GA, USA.

Jar-How Lee (JH)

Terasaki Innovation Center, Los Angeles, CA, USA. jarhowlee@tictx.org.

Classifications MeSH