Full-length HLA class II sequences
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ABSTRACT:
PROVIDER: PRJEB42469 | ENA |
REPOSITORIES: ENA
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Project description:Prediction of HLA epitopes is important for the development of cancer immunotherapies and vaccines. However, current prediction algorithms have limited predictive power, in part because they were not trained on high-quality epitope datasets covering a broad range of HLA alleles. To enable prediction of endogenous HLA class I-associated peptides across a large fraction of the human population, we used mass spectrometry to profile >185,000 peptides eluted from 95 HLA-A, -B, -C and -G mono-allelic cell lines. We identified canonical peptide motifs per HLA allele, unique and shared binding submotifs across alleles and distinct motifs associated with different peptide lengths. By integrating these data with transcript abundance and peptide processing, we developed HLAthena, providing allele-and-length-specific and pan-allele-pan-length prediction models for endogenous peptide presentation. These models predicted endogenous HLA class I-associated ligands with 1.5-fold improvement in positive predictive value compared with existing tools and correctly identified >75% of HLA-bound peptides that were observed experimentally in 11 patient-derived tumor cell lines.
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Project description:Full length HLA sequencing of cell lines to provide the histocompatibility and immunogenetics field with ultra-high resolution typing of vital reference sources.
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Project description:Gene expression analysis of molecules with known function in HLA class II antigen processing and presentation. Various hematopoietic cell types and (cytokine pre-treated) non-hematopoietic cells that are targeted in Graft-versus-Leukemia reactivity and Graft-versus-Host Disease were collected. Expression was compared between the different hematopoietic and non-hematopoietic cell types for the Invariant chain, HLA-DMA, HLA-DMB, HLA-DOA and HLA-DOB genes. The data show that the Invariant chain, HLA-DMA, HLA-DMB and HLA-DOA genes are expressed in all or the majority of cell types with HLA class II surface expression, whereas expression of the HLA-DOB gene is restricted to professional antigen presenting B-cells and mature dendritic cells. Total RNA was isolated from various hematopoietic cell types isolated (and cultured) from (G-CSF mobilized) peripheral blood from five different individuals and from (IFN-g pre-treated) fibroblasts cultured from skin biopsies from four different patients transplanted with allogeneic hematopoietic stem cells.
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Project description:Gene expression analysis of molecules with known function in HLA class II antigen processing and presentation. Various hematopoietic cell types and (cytokine pre-treated) non-hematopoietic cells that are targeted in Graft-versus-Leukemia reactivity and Graft-versus-Host Disease were collected. Expression was compared between the different hematopoietic and non-hematopoietic cell types for the Invariant chain, HLA-DMA, HLA-DMB, HLA-DOA and HLA-DOB genes. The data show that the Invariant chain, HLA-DMA, HLA-DMB and HLA-DOA genes are expressed in all or the majority of cell types with HLA class II surface expression, whereas expression of the HLA-DOB gene is restricted to professional antigen presenting B-cells and mature dendritic cells.
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Project description:Major Histocompatibility Complex Class II antigen presentation underlies a wide range of immune responses in health and disease. Although peptide ligand binding affinity has been the major focus for explaining and predicting class II antigens, we know that the levels and activities of accessory molecules, HLA-DM (DM) and HLA-DO (DO) can have strong effects on peptide repertoires. However, the extent to which these antagonistic proteins’ levels relative to one another shape the identities and properties of peptides selected for presentation remains unclear. Hence, after creating cell line panel with varying DO:DM ratios, of we set out to measure the effects these ratios can have on peptide presentation. Using a combined immunopeptidomic and proteomic discovery strategy, we profiled ligandome differences across this panel. By surveying over 10,000 unique HLA-DR4-presented peptides, we found marked increases in repertoire diversity and altered physical properties of presented peptides that corresponded with increasing DO:DM ratios.
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Project description:New full-length MHC class II alleles in the chimpanzee (Pan troglodytes).
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