Date of Award

Fall 2021

Publication Type

Thesis

Degree Name

M.Sc.

Department

Chemistry and Biochemistry

Keywords

Autoimmune diseases, Human leukocyte antigen, Human cartilage glycoprotein, Citrullination

Supervisor

J. Trant

Supervisor

Y. Tong

Rights

info:eu-repo/semantics/openAccess

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

Abstract

Autoimmune diseases occurs when the immune system recognize self antigens in the body as foreign invaders leads to dysfunction of tissue. RA is an autoimmune disease, caused by improper recognition of self-peptides, particularly human cartilage glycoprotein and type II collagen, by specific human leukocyte antigen (HLA) receptors. Normally T-cell specific for these peptides are destroyed in the thymus before they are released, preventing autoimmunity. However, certain post-translational modifications, especially citrullination, can lead to “self-peptide” recognition by non-self T cells: in the case of RA, one HLA protein (DRB*0401), out of about 1700 possible ones, is responsible for 65% of RA cases. If this protein could be blocked, drugs could be developed that interrupt the disease at its root cause without affecting the rest of the immune system; this is the focus of research in the Trant Lab. This thesis will briefly overview the approach, including the drug design, and will focus on the molecular biology work accomplished to date. The main finding of our thesis are as follows. Human leukocyte antigen is a protein needed to advance the research and drug development in autoimmune diseases and cancers. In these early stages of this project, we showed that choice of HEK293 cell as a host to express HLA protein and IMAC chromatography as a purification system gives us a reasonable amount of α/β heterodimer glycosylated membrane HLA protein.

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