All ETDs from UAB

Advisory Committee Chair

Robin Lorenz

Advisory Committee Members

Alfred J Tector

Anupam Agarwal

David Kc Cooper

Roslyn Mannon

Matthew Tector

Document Type

Dissertation

Date of Award

2018

Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine

Abstract

Xenotransplantation, using genetically-modified pigs as organ donors, is a potential solution to the growing transplant organ shortage. Avoiding antibody-mediated rejection (AMR) is the remaining hurdle to widespread application. The development of a triple glycan knockout pig reduced antibody binding to clinically acceptable levels, allowing for the screening of the history of antibodies to the major histocompatibility complex (MHC). In allotransplantation, the MHC is a group of proteins divided into two classes and anti-MHC antibodies possess the ability to cause both acute and chronic AMR. The pig MHC, the swine leukocyte antigen (SLA), is a hypothesized target of antibodies. This dissertation developed several models to screen human sera for anti-SLA class II antibodies. The findings suggest that SLA class II is a target of antibodies, and these antibodies are specific to certain SLA class II proteins, cytotoxic, and bind conserved amino acid epitopes found in the pig and human MHC. Genetic engineering of these epitopes is potential strategy to decrease human sera antibody binding without compromising pig immunity. This approach would provide transplant patients highly sensitized to the human MHC with a non-immunoreactive pig organ donor.

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