A method for enhancing t cell response
A technology of cells and cytokines, applied in the field of immunology and vaccine development, can solve problems such as weak T cells and reduced antigenic patterns of vaccines
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Embodiment 1
Example 1: Materials and methods
[0091] Mice. 6-12 week old C57BL / 6 mice were purchased from Harlan (Horst, Netherlands). TCR318 transgenic mice were obtained from Cytos Biotechnology AG (Schlieren, Switzerland), which express a T-cell receptor specific for the peptide gp33 (aa33-41), which represents the bPredominant immune epitope of lymphocytic choriomeningitis virus (LCMV) located in glycoprotein in mouse (Pircher, H., et al. 1989. Nature (natural) 342:559-561; Pircher, H. . et al., Nature 346, 629-633, 1990, each of which is incorporated herein by reference in its entirety). HHD transgenic mice expressing HLA A2.1 were initially obtained from MannKind Corporation (MannKind Company) (Valencia, CA; Pascolo, S. et al., J Exp Med (Journal of Experimental Medicine) 185, 2043-2051, 1997, the entire content of which incorporated herein by reference). Mice were bred and maintained in a specific pathogen-free facility at the University Hospital in Zurich according to the regul...
Embodiment 2
[0103] It was investigated whether T cell responses could be enhanced by increasing antigen stimulation. In the first experiment, the 1x10 6 Transgenic gp33-specific T cells were transferred into C57BL / 6 wild-type recipient mice to increase the frequency of precursor T cells and facilitate the assessment of immune responses.
[0104] use figure 1 D and different vaccination schemes disclosed in Table 1, all mice were immunized with the same cumulative dose of gp33 peptide mixed with CpGODN (total 125 μg gp33 and 12.5 nmol CpG): s1) single dose bolus injection on day 0; s2 ) four equal doses over four days; s3) reduced doses over four days; and s4) increased doses over four days. In addition, groups of mice were immunized with a single dose of CpG followed by exponentially increasing doses of the gp33 peptide (s5), or with a single dose of gp33 followed by exponentially increasing doses of CpG (s6). Mice infected intravenously with 250 pfu of LCMV virus on day 0 served as po...
Embodiment 3
Example 3: CD8 + Enhancement of T cell responses independent of T cell helper
[0111] with CD8 + The role of T-helper in relation to T cell priming is well known in the art. Th epitope may be responsible for functional CD8 + T cell immunity is critical (Johansen et al., Eur J Immunol., 34, 91-97, 2004; Shedlock and Shen, Science, 300, 337-339, 2003; Sun and Bevan , Science (Science), 300, 339-342, 2003, each of which is incorporated herein by reference in its entirety). On the other hand, in the case of high precursor frequency, CD8 + T cell responses are less Th-dependent (Mintern et al., J Immunol., 168, 977-980, 2002, the entire contents of which are hereby incorporated by reference), especially when using strong immunogens such as , LCMV gp33. Furthermore, the route of administration can also affect the requirement for T-help (Bour et al., J Immunol., 160, 5522-5529, 1998, the entire contents of which are incorporated herein by reference). Therefore, the Th-dependen...
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