A single-chain H-2Db molecule presenting an influenza virus nucleoprotein epitope shows enhanced ability at stimulating CD8+ T cell responses in vivo.

Palmowski, M; Parker, M; Choudhuri, K; Chiu, C; Callan, M; Van Der Merwe, P; Cerundolo, V; Gould, K

Journal article

A single-chain H-2Db molecule presenting an influenza virus nucleoprotein epitope shows enhanced ability at stimulating CD8+ T cell responses in vivo.

Abstract:: We have generated a construct encoding a single-chain H-2D(b) mouse MHC class I molecule in which an influenza virus nucleoprotein (NP) epitope, amino acid sequence ASNENMDAM, is fused to mouse beta(2)-microglobulin and the D(b) H chain via flexible linker sequences. This single-chain trimer (SCT) was efficiently expressed at the cell surface independently of TAP and endogenous beta(2)-microglobulin, and it was recognized directly and efficiently by specific T cells in vitro. A recombinant vaccinia virus encoding the D(b) NP SCT primed a CD8(+) T cell response in C57BL/6 mice 4-fold greater than an equivalent virus expressing the NP epitope as a minigene, as shown by tetramer staining, whether or not the minigene was directed into the endoplasmic reticulum by a signal sequence. This response was functional as shown by in vivo lysis assays with peptide-pulsed target cells, and it was greatly expanded following secondary challenge in vivo with influenza virus. The SCT was also significantly more immunostimulatory for CD8(+) cells than the NP minigene in adoptive transfer experiments using F5 TCR transgenic spleen cells, in which the magnitude of the T cell response was much greater. Our results extend previous DNA vaccination studies using SCTs, which demonstrated that such molecules are capable of generating functional CD8(+) T cell responses. We have shown that class I SCTs are more immunogenic than even preprocessed Ag in the form of an epitope minigene, and they therefore should be considered for use when the generation of optimal CD8(+) T cell responses is required.

Publication status:: Published

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APA Style

Palmowski, M., Parker, M., Choudhuri, K., Chiu, C., Callan, M., Van Der Merwe, P., Cerundolo, V., & Gould, K. (2009). A single-chain H-2Db molecule presenting an influenza virus nucleoprotein epitope shows enhanced ability at stimulating CD8+ T cell responses in vivo. Journal of Immunology, 182(8), 4565–4571.

MLA Style

Palmowski, M., et al. “A Single-Chain H-2Db Molecule Presenting an Influenza Virus Nucleoprotein Epitope Shows Enhanced Ability at Stimulating CD8+ T Cell Responses in Vivo.” Journal of Immunology, vol. 182, no. 8, 2009, pp. 4565–71.

Chicago Style

Palmowski, M, M Parker, K Choudhuri, C Chiu, M Callan, P Van Der Merwe, V Cerundolo, and K Gould. 2009. “A Single-Chain H-2Db Molecule Presenting an Influenza Virus Nucleoprotein Epitope Shows Enhanced Ability at Stimulating CD8+ T Cell Responses in Vivo.” Journal of Immunology 182 (8): 4565–71.
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