Promiscuity of Peptides Presented in HLA-DP Molecules from Different Immunogenicity Groups Is Associated With T-Cell Cross-Reactivity.

Autor:	Laghmouchi A; Department of Hematology, Leiden University Medical Center, Leiden, Netherlands., Kester MGD; Department of Hematology, Leiden University Medical Center, Leiden, Netherlands., Hoogstraten C; Department of Hematology, Leiden University Medical Center, Leiden, Netherlands., Hageman L; Department of Hematology, Leiden University Medical Center, Leiden, Netherlands., de Klerk W; Department of Hematology, Leiden University Medical Center, Leiden, Netherlands., Huisman W; Department of Hematology, Leiden University Medical Center, Leiden, Netherlands., Koster EAS; Department of Hematology, Leiden University Medical Center, Leiden, Netherlands., de Ru AH; Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, Netherlands., van Balen P; Department of Hematology, Leiden University Medical Center, Leiden, Netherlands., Klobuch S; Department of Hematology, Leiden University Medical Center, Leiden, Netherlands., van Veelen PA; Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, Netherlands., Falkenburg JHF; Department of Hematology, Leiden University Medical Center, Leiden, Netherlands., Jedema I; Department of Hematology, Leiden University Medical Center, Leiden, Netherlands.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2022 Feb 16; Vol. 13, pp. 831822. Date of Electronic Publication: 2022 Feb 16 (Print Publication: 2022).
DOI:	10.3389/fimmu.2022.831822
Abstrakt:	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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Laghmouchi, Kester, Hoogstraten, Hageman, de Klerk, Huisman, Koster, de Ru, van Balen, Klobuch, van Veelen, Falkenburg and Jedema.)
Databáze:	MEDLINE
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