Understanding the post-translational control of CD86 in regulating T cell stimulation AND What is the role of Lyp phosphatase (PTPN22) in phagocyte signaling?

Halford, Emily Elisabeth (2012). Understanding the post-translational control of CD86 in regulating T cell stimulation AND What is the role of Lyp phosphatase (PTPN22) in phagocyte signaling? University of Birmingham. M.Res.

Preview

Halford12MRes.pdf
PDF - Accepted Version
Download (3MB)

Abstract

Background: T cell activation requires two signals, the first of which is provided by the interaction between the TCR and MHC-peptide complex and the second which is provided by the interaction between CD86 and CD28. CD86 is upregulated on antigen presenting cells (APCs) upon encounter with pathogen, and therefore its expression acts as a critical checkpoint for T cell activation. MARCH 1 and 8 ligases have been shown to regulate CD86 expression via a post-translational mechanism in immature APCs, preventing the balance of T cell activation versus anergy being shifted and auto-reactive T cells potentially becoming activated.

Methods: Cyclohexamide, an inhibitor of protein synthesis, was used to investigate the stability of CD86 on the surface of human APCs and MARCH 1 and 8 ligases were overexpressed in Chinese Hamster Ovary (CHO)-CD86 cells.

Results: Overexpression led to a 98-99% decrease in the level of surface CD86. This was shown to be via endocytosis and was associated with a high level of ubiquitination. However CD86 was found to be stable on human APCs.

Conclusions: These results demonstrate the potential for potent downregulation of CD86 by
MARCH 1 and 8 and raise questions about how such a mechanism operates and is regulated in primary cells.

Type of Work:

Thesis (Masters by Research > M.Res.)

Award Type:

Masters by Research > M.Res.

Supervisor(s):