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

被引:8
|
作者
Laghmouchi, Aicha [1 ]
Kester, Michel G. D. [1 ]
Hoogstraten, Conny [1 ]
Hageman, Lois [1 ]
de Klerk, Wendy [1 ]
Huisman, Wesley [1 ]
Koster, Eva A. S. [1 ]
de Ru, Arnoud H. [2 ]
van Balen, Peter [1 ]
Klobuch, Sebastian [1 ]
van Veelen, Peter A. [2 ]
Falkenburg, J. H. Frederik [1 ]
Jedema, Inge [1 ]
机构
[1] Leiden Univ, Dept Hematol, Med Ctr, Leiden, Netherlands
[2] Leiden Univ, Med Ctr, Ctr Prote & Metab, Leiden, Netherlands
来源
FRONTIERS IN IMMUNOLOGY | 2022年 / 13卷
关键词
AlloSCT; HLA-DP; peptidome; DPC-classification; CD4 T-cell clones; cross-reactivity; VERSUS-HOST-DISEASE; LEUKEMIA REACTIVITY; HLA-DPB1; DISPARITY; GRAFT; TRANSPLANTATION; MISMATCHES; EXPRESSION; RECIPIENTS; SELECTION; DEPENDS;
D O I
10.3389/fimmu.2022.831822
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
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页数:10
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