Targeting allogeneic HLA-DP: diversity, specificity and magnitude of T-cell responses

Following HLA-DP-mismatched alloSCT and DLI, donor T cells show allogeneic (allo) HLA-DP-specific reactivity, resulting in a graft-versus-leukemia (GvL) effect with or without coinciding graft-versus-host disease (GvHD). The contribution of alloHLA-DP-specific T cells to the occurrence of GvL and GvHD may depend on several factors including the expression of HLA-DP on hematopoietic and non-hematopoietic patient cells and the magnitude of the allo-HLA-DP-specific immune responses. The magnitude of the allo-HLA-DP-specific immune responses provoked by HLA-DP-mismatched antigen-presenting cells (APC) is influenced by the immunogenicity of the mismatched target HLA-DP allele(s) and the specificity and diversity of allo-HLA-DP-specific T-cell repertoires. In this thesis, we investigated in vitro the composition of allo-HLA-DP-specific T-cell repertoires and the magnitude and diversity of allo-HLA-DP-specific immune responses provoked under different stimulatory conditions.