Project description:A high-throughput mass spectrometry analysis was used to identify more than 16,000 cell peptides bound to several HLA-DR and -DP class II molecules isolated from large amounts of two human cell lines (HOM-2 and JY).
Project description:Negative control (healthy cells) of MSV000079647. HLA-DR ligands from healthy Jy cells. Using mass spectrometry analysis of complex HLA class II-bound peptide pools isolated from large amounts of non-infected cells were identified.
Project description:Analysis of the peptide repertoires eluted from different HLA-DP molecules expressed in HeLa cells co-expressing Invariant chain either with or without HLA-DM as components of the HLA class II processing machinery. Divergence of the immunopeptidomes and the impact of HLA-DM were investigated in relation to the capacity of HLA-DP molecules to elicit alloreactive T-cell responses.
Project description: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.
Project description:HLA-DR ligands from HRSV-infected cells. Using mass spectrometry analysis of complex HLA class II-bound peptide pools isolated from large amounts of HRSV-infected cells, nineteen naturally processed HLA-DR ligands, most of them included in complex nested set of peptides, were identified.