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Journal Article

Releasing the concept of HLA-allele specific peptide anchors in viral infections: A non-canonical naturally presented human cytomegalovirus-derived HLA-A*24:02 restricted peptide drives exquisite immunogenicity.

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Huyton,  T.
Department of Cellular Logistics, MPI for Biophysical Chemistry, Max Planck Society;

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3074264.pdf
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3074264_Suppl_1.docx
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3074264_Suppl_2.docx
(Supplementary material), 204KB

3074264_Suppl_3.docx
(Supplementary material), 73KB

Citation

Pump, W. C., Schulz, R., Huyton, T., Kunze-Schumacher, H., Martens, J., Ho, G. G. T., et al. (2019). Releasing the concept of HLA-allele specific peptide anchors in viral infections: A non-canonical naturally presented human cytomegalovirus-derived HLA-A*24:02 restricted peptide drives exquisite immunogenicity. HLA: Immune Response Genetics, 94(1), 25-38. doi:10.1111/tan.13537.


Cite as: http://hdl.handle.net/21.11116/0000-0003-DDC7-4
Abstract
T-cell receptors possess the unique ability to survey and respond to their permanently modified ligands, self HLA-I molecules bound to non-self peptides of various origin. This highly specific immune function is impaired following hematopoietic stem cell transplantation (HSCT) for a timespan of several months needed for the maturation of T-cells. Especially, the progression of HCMV disease in immunocompromised patients induces life-threatening situations. Therefore, the need for a new immune system that delivers vital and potent CD8+ T-cells carrying TCRs that recognize even one human cytomegalovirus (HCMV) peptide/HLA molecule and clear the viral infection long term becomes obvious. The transcription and translation of HCMV proteins in the lytic cycle is a precisely regulated cascade of processes, therefore, it is a highly sensitive challenge to adjust the exact time point of HCMV-peptide recruitment over self-peptides. We utilized soluble HLA technology in HCMV-infected fibroblasts and sequenced naturally sHLA-A*24:02 presented HCMV-derived peptides. One peptide of 14 AAs length derived from the IE2 antigen induced the strongest T-cell responses; this peptide can be detected with a low ranking score in general peptide prediction databanks. These results highlight the need for elaborate and HLA-allele specific peptide selection.