| Reference |
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| Reference Type | Literature | IEDB_Reference:1040629 |
| Title | Promiscuity of Peptides Presented in HLA-DP Molecules from Different Immunogenicity Groups Is Associated With T-Cell Cross-Reactivity. | |
| Authors | Aicha Laghmouchi; Michel G D Kester; Conny Hoogstraten; Lois Hageman; Wendy de Klerk; Wesley Huisman; Eva A S Koster; Arnoud H de Ru; Peter van Balen; Sebastian Klobuch; Peter A van Veelen; J H Frederik Falkenburg; Inge Jedema | |
| Affiliations | Department of Hematology, Leiden University Medical Center, Leiden, Netherlands; Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, Netherlands. | |
| Journal | Front Immunol | |
| Year | 2022 | |
| Abstract | In the context of HLA-DP-mismatched allogeneic stem cell transplantation, mismatched HLA-DP alleles can provoke profound allo-HLA-DP-specific immune responses from the donor T-cell repertoire leading to graft-versus-leukemia effect and/or graft-versus-host disease in the patient. The magnitude of allo-HLA-DP-specific immune responses has been shown to depend on the specific HLA-DP disparity between donor and patient and the immunogenicity of the mismatched HLA-DP allele(s). HLA-DP peptidome clustering (DPC) was developed to classify the HLA-DP molecules based on similarities and differences in their peptide-binding motifs. To investigate a possible categorization of HLA-DP molecules based on overlap of presented peptides, we identified and compared the peptidomes of the thirteen most frequently expressed HLA-DP molecules. Our categorization based on shared peptides was in line with the DPC classification. We found that the HLA-DP molecules within the previously defined groups DPC-1 or DPC-3 shared the largest numbers of presented peptides. However, the HLA-DP molecules in DPC-2 segregated into two subgroups based on the overlap in presented peptides. Besides overlap in presented peptides within the DPC groups, a substantial number of peptides was also found to be shared between HLA-DP molecules from different DPC groups, especially for groups DPC-1 and -2. The functional relevance of these findings was illustrated by demonstration of cross-reactivity of allo-HLA-DP-reactive T-cell clones not only against HLA-DP molecules within one DPC group, but also across different DPC groups. The promiscuity of peptides presented in various HLA-DP molecules and the cross-reactivity against different HLA-DP molecules demonstrate that these molecules cannot be strictly categorized in immunogenicity groups. | |
| External Link | | PXD030591 |
| Curation Last Updated | 2024-09-17 03:00:39 | |