Session Time: 3:15pm-4:45pm
Presentation Time: 3:51pm-4:03pm
*Purpose: BKPyV persists as significant cause of premature kidney transplant failure. Current treatment is based on reducing immunosuppression to regain immune control over BKPyV replication [1, 2]. BKPyV-specific T cells have been shown to play a major role in this regard, whereby increasing cytotoxic CD8 T cells have been associated with clearance of BKPyV-DNAemia . We aimed at characterising the role of antigen-presenting cells (APCs), CD4 T cells and adjuvants in boosting peptide-specific BKPyV-specific CD8+T cell responses in vitro.
*Methods: 25 BKPyV-Vp1-VLP IgG ELISA seropositive blood donors (BD) were HLA-typed using NGS sequencing. Cryopreserved PBMCs were differentiated into monocyte-derived dendritic cells (Mo-DCs) and monocyte-derived Langerhans cells (Mo-LCs). Mo-DCs and Mo-LCs were pulsed with overlapping 15mer peptide pools (15mP) covering the BKPyV large Tumor-antigen (LTag) and co-cultured with autologous T cells. Cells were re-stimulated either with 15mP or the 9mP containing 97 immunodominant 9mer epitopes . BKPyV-specific T cell responses were measured using IFNy-ELISpot and FACS.
*Results: Mo-LCs induced higher overall BKPyV-specific CD4 T cell responses than Mo-DCs, whereas overall CD8 T cell responses were similar, with some exceptions (Figure 1A). BKPyV-specific CD8 T cell responses required CD4 T cell help, since selective CD4 T cell removal showed significant reductions in CD8 T cell IFNy-responses (Figure 1B). Using MF59-adjuvant, BKPyV-specific T cell responses were increased in 3 individuals among the 6 donors tested. Notably, HLA-B7 and HLA-B8 BD (n=2) showed higher CD8 T cell responses to the immunodominant 9m127 peptide in the presence of adjuvant .
*Conclusions: Our data indicate the peptide-dependent increase of CD8 T cells responses using rational combinations of peptides, APCs, CD4 T cells and adjuvant. The relevance for peptide-specific vaccines will be evaluated.
 Hirsch HH, Randhawa PS, AST-IDCOP (2019) Clin Transplant: e13528;  Kaur A et al (2019) Curr Opin Infect Dis 32: 575;  Leboeuf C et al (2017) Am J Transplant 17: 2591;  Cioni M et al (2016) Am J Transplant 16: 1193;  Wilhelm M et al (2019) Transplantation 103: e384;
To cite this abstract in AMA style:Wilhelm M, Kaur A, Wernli M, Hirsch HH. Role of Peptide Antigen, Antigen-Presenting Cells and CD4 T Cells in Modulating BK Polyomavirus (BKPyV)-Specific CD8 T Cell Responses In Vitro [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/role-of-peptide-antigen-antigen-presenting-cells-and-cd4-t-cells-in-modulating-bk-polyomavirus-bkpyv-specific-cd8-t-cell-responses-in-vitro/. Accessed April 15, 2021.
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