Generation of cytotoxicity against hepatitis delta virus genotypes and quasispecies by epitope modification

Huang, Yi Hsiang; Wu, Jaw Ching; Peng, Wei; Huo, Teh Ia; Shih, Hsuan Hui; Lan, Keng‐Li; Su, Chien Wei; Lee, Shou Dong

doi:10.1016/j.jhep.2008.11.028

Cited by 4 publications

(2 citation statements)

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“…CD8 + T cells raised with this epitope can recognize a range of cross-reactive peptide/MHC complexes. Several studies reported that tyrosine substitution at position 1 of an HLA-A2-restricted CTL epitope could increase its binding affinity and did not interfere with TCR interaction [32], [41], [42]. We also found that CD8 + T cells induced by POTE-553-1Y cross-reactively recognized wild type POTE 553 peptide/MHC class I complex as well as POTE-expressing human cancer cells, NCI-H522.…”

Section: Discussionsupporting

confidence: 62%

“…Substitution of Leu at position 9 with Val, and Lys at position 1 with Tyr in POTE 252 moderately improved the peptide binding affinity to HLA-A2 molecules. This could be explained by the fact that Val is the optimal AA for the C-terminal anchor residue for HLA-A2-binding peptides, and Tyr in position 1 was reported to stabilize the binding of peptide/MHC complex [7], [32], [41], [42]. The immunogenicity of the wild type and enhanced peptides was compared by using AAD and HHD-2 transgenic mice.…”

Section: Discussionmentioning

confidence: 99%

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Identification and Enhancement of HLA-A2.1-Restricted CTL Epitopes in a New Human Cancer Antigen-POTE

et al. 2013

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Identification of CD8+ T cell epitopes that can induce T cells to kill tumor cells is a fundamental step for development of a peptide cancer vaccine. POTE protein is a newly identified cancer antigen that was found to be expressed in a wide variety of human cancers, including prostate, colon, lung, breast, ovary and pancreas. Here, we determined HLA-A2.1-restricted cytotoxic T lymphocyte (CTL) epitopes in the POTE protein, and also designed enhanced epitopes by amino acid (AA) substitutions. Five 9-mer peptides were first selected and their binding affinity to HLA-A2 molecules was measured by the T2 binding assay. POTE 272–280 and POTE 323–331 showed the strongest HLA-A2 binding affinity. AA substituted peptides POTE 252-9V (with valine at position 9), POTE 553-1Y (with tyrosine at position 1) and POTE 323-3F (with phenylalanine at position 3) conferred higher affinity for HLA-A2, and induced CTL responses cross-reactive with wild type antigens. While POTE 252-9V was the strongest in this respect, POTE 323-3F had the greatest increase in immunogenicity compared to wild type. Importantly, two modified epitopes (POTE-553-1Y and POTE-323-3F) induced CTLs that killed NCI-H522, a POTE-expressing HLA-A2+ human non-small cell lung cancer cell line, indicating natural endogenous processing of these epitopes. In conclusion, the immunogenicity of POTE epitopes can be enhanced by peptide modification to induce T cells that kill human cancer cells. A combination of POTE 553-1Y and POTE 323-3F epitopes might be an attractive vaccine strategy for HLA-A2 cancer patients to overcome tolerance induced by tumors and prevent escape.

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Section: Discussionsupporting

confidence: 62%