2020Leiden Repository (Leiden University)Open access

Towards HLA epitope matching in clinical transplantation

Cynthia S. M. Kramer

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Abstract

In recent years HLA epitope matching is becoming a hot topic in transplant community to prevent donor-specific antibody formation after transplantation, as such antibodies are associated with inferior graft survival. The number of HLA epitope mismatches between donor and recipient correlates with donor-specific antibody formation, but not every epitope mismatch will trigger an antibody response. Therefore, it is pivotal to define the immunogenic epitopes. In my thesis we describe the development of the software HLA-EMMA to determine HLA amino acid mismatches between donor and recipient to identify immunogenic amino acids. In addition, the generation of recombinant human HLA-DR monoclonal antibodies for antibody-verification of eplets/epitopes is described. These tools will contribute to the definition of immunogenic epitopes, which is required before introducing HLA epitope matching in the clinic.

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In recent years HLA epitope matching is becoming a hot topic in transplant community to prevent donor-specific antibody formation after transplantation, as such antibodies are associated with inferior graft survival. The number of HLA epitope mismatches between donor and recipient correlates with donor-specific antibody formation, but not every epitope mismatch will trigger an antibody response. Therefore, it is pivotal to define the immunogenic epitopes. In my thesis we describe the development of the software HLA-EMMA to determine HLA amino acid mismatches between donor and recipient to identify immunogenic amino acids. In addition, the generation of recombinant human HLA-DR monoclonal antibodies for antibody-verification of eplets/epitopes is described. These tools will contribute to the definition of immunogenic epitopes, which is required before introducing HLA epitope matching in the clinic.

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Available abstract

In recent years HLA epitope matching is becoming a hot topic in transplant community to prevent donor-specific antibody formation after transplantation, as such antibodies are associated with inferior graft survival. The number of HLA epitope mismatches between donor and recipient correlates with donor-specific antibody formation, but not every epitope mismatch will trigger an antibody response. Therefore, it is pivotal to define the immunogenic epitopes. In my thesis we describe the development of the software HLA-EMMA to determine HLA amino acid mismatches between donor and recipient to identify immunogenic amino acids. In addition, the generation of recombinant human HLA-DR monoclonal antibodies for antibody-verification of eplets/epitopes is described. These tools will contribute to the definition of immunogenic epitopes, which is required before introducing HLA epitope matching in the clinic.

Key concepts: Epitope, Human leukocyte antigen, Monoclonal antibody, Antibody, Transplantation, Immunology, Epitope mapping, Virology

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