Part:BBa_K4469015

CMV pp65 NLVPMVATV (residues 495-503)

Cymegalovirus (CMV) 65kDa phosphoprotein (pp65) antigen derived nonamer NLVPMVATV (residues 495-503) is predominantly displayed on HLA-A*02:01, which is the most abundant MHC-I variant in human population. CMV pp65 is selected for its non-human origin, thereby reducing the on-target off-tumour effects caused by conventional CAR-T therapy, which targeted antigens that could be found in both healthy and tumor cells. In addition, CMV pp65 is able to evoke cytotoxic T lymphocyte (CTL) response, with the NLVPMVATV as the most immunogenic epitope. CMV is asymptomatic in healthy individuals, while its seroprevalence is around 70% in industrialized countries and up to 100% in emerging countries. Infected subjects have shown high frequencies of HCMV-CTL positivity, with 70-90% of them specifically recognizing pp65 protein. Isolated from the 65kDa-protein, residue 495-503 could be used to amplify a memory CTL response. 40% of NLVPMVATV sensitized fibroblast was lysed by CTL from HCMV seropositive individuals in vitro.

Reference

Diamond, D. J., York, J., Sun, J.-Y., Wright, C. L., & Forman, S. J. (1997). Development of a candidate HLA A*0201 restricted peptide-based vaccine against human cytomegalovirus infection. Blood, 90(5), 1751–1767. https://doi.org/10.1182/blood.v90.5.1751

Diamond, D. J., York, J., Sun, J.-Y., Wright, C. L., & Forman, S. J. (1997). Development of a candidate HLA A*0201 restricted peptide-based vaccine against human cytomegalovirus infection. Blood, 90(5), 1751–1767. https://doi.org/10.1182/blood.v90.5.1751

Hyun, S.-J., Sohn, H.-J., Lee, H.-J., Lee, S.-D., Kim, S., Sohn, D.-H., Hong, C.-H., Choi, H., Cho, H.-I., & Kim, T.-G. (2017). Comprehensive analysis of cytomegalovirus PP65 antigen-specific CD8+ T cell responses according to human leukocyte antigen class I allotypes and intraindividual dominance. Frontiers in Immunology, 8. https://doi.org/10.3389/fimmu.2017.01591

Wills, M. R., Carmichael, A. J., Mynard, K., Jin, X., Weekes, M. P., Plachter, B., & Sissons, J. G. (1996). The human cytotoxic T-lymphocyte (CTL) response to cytomegalovirus is dominated by structural protein PP65: Frequency, specificity, and T-cell receptor usage of PP65-specific CTL. Journal of Virology, 70(11), 7569–7579. https://doi.org/10.1128/jvi.70.11.7569-7579.1996

Sequence and Features

Assembly Compatibility:

• 10
  COMPATIBLE WITH RFC[10]
• 12
  COMPATIBLE WITH RFC[12]
• 21
  COMPATIBLE WITH RFC[21]
• 23
  COMPATIBLE WITH RFC[23]
• 25
  COMPATIBLE WITH RFC[25]
• 1000
  COMPATIBLE WITH RFC[1000]