From clones to immunopeptidomes: New developments in the characterization of permissive HLA-DP mismatches in hematopoietic cell transplantation

• Published in: Best practice & research. Clinical haematology 2024-09, Vol.37 (3), p.101575, Article 101575
• Main Author: Arrieta-Bolaños, Esteban
• Format: Article
• Language: English
• Subjects: Core T-cell epitope groups; Directionality; Epitopes, T-Lymphocyte - immunology; Graft vs Host Disease - immunology; GvHD; Hematopoietic Stem Cell Transplantation; Histocompatibility Testing - methods; HLA-DP; HLA-DP beta-Chains - genetics; HLA-DP beta-Chains - immunology; Humans; Immunopeptidome; NRM; Permissive mismatches; Relapse; T-Lymphocytes - immunology; Unrelated Donors; Unrelated HCT
• ISSN: 1521-6926; 1532-1924; 1532-1924
• DOI: 10.1016/j.beha.2024.101575

Mismatching at the HLA-DPB1 locus occurs frequently in hematopoietic cell transplantation with unrelated donors. Despite this, HLA-DPB1 allelic mismatches have traditionally not been considered in patient-donor matching. A T-cell epitope (TCE) model for the functional assessment of permissive mismatches at this locus has nevertheless been adopted in clinical practice. While initially based on a hierarchical immunogenicity elucidated from allorecognition by T-cell clones isolated from a patient, newer developments in the understanding of this model's biological basis, including a central role for immunopeptidome divergence between mismatched allotypes, have prompted changes in the assignment of permissiveness, providing the opportunity for a more granular evaluation of graft-versus-host disease and relapse risks according to the nature and directionality of permissive mismatches. How these advances impact the assessment of permissiveness at HLA-DPB1 and potentially the intelligent selection of donors according to the main clinical goal for different patients is the subject of the present review.