BIOCHEMISTRY AND CHEMICAL BIOLOGY OF THE IMMUNE SYSTEM (DR. E. STRATIKOS)

(Picture from https://joel-kowit.squarespace.com/)

ER AMINOPEPTIDASES AND THE IMMUNE RESPONSE

The adaptive immune response relies on the presentation of small peptide-antigen fragments onto specialised cell-surface receptors (MHC molecules) for recognition by cytotoxic T-lymphocytes. These peptides are generated from the degradation of intra or extra cellular proteins. Intracellular aminopeptidases like ERAP1, ERAP2 and IRAP play a crucial role in antigenic peptide generation and affect quantitative and qualitative aspects of the immune response (for more information click here, also read this paper and this paper).

Naturally occurring polymorphisms (SNPs) on ERAP1/2 have been linked with predisposition to autoimmune diseases like Ankylosing Spondylitis and Diabetes as well as susceptibility to viral and bacterial infections and tumour development. How ERAP1 SNPs affect disease predisposition and pathogenesis in not known, but it has been hypothesised that aberrant antigen presentation may be the mechanism behind these effects. We are currently evaluating the diagnostic and prognostic value of these SNPs by studying their effects on protein function and antigen processing. We are also developing small molecular-weight inhibitors for these molecules in an effort to control their enzymatic activity in vivo for immunotherapy applications and as tools to be used to investigate molecular aspects of immune regulation.

More details on ongoing research projects can be found below:

• Molecular analysis of antigen processing and presentation

• Mechanisms of aminopeptidase function

• Modulating antigen processing for cancer immunotherapy

• Rational drug-design for molecules that regulate antigen presentation

Please visit this site for more information.