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

Author(s):
Laghmouchi, A.
Published
2022
Publication type
Doctoral Thesis

Abstract

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.

Allogeneic stem cell transplantation (alloSCT)Graft-versus-leukemia effect (GvL)Graft-versus-host disease (GvHD)HLA-DP mismatchIn vitro T-cell responsesAllo-HLA-DP reactivityTissue- and cell type-restricted specificitiesHLA-DP immunogenicity groups
Defense date
2022-10-06
Language
English
Supervisor(s)
Falkenburg, J.H.F.
Advisor(s)
Jedema, I.
Committee member(s)
Zwaginga, J.J.; Koning, F.; Hazenberg, M.D.; Dolstra, H.
Qualification
Ph.D.
Degree granting institution
Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University, Leiden
hdl
1887/3466105
ISBN(s)
9789083255620