Immune self-reactivity triggered by carbamazepine-modified HLA-peptide repertoire

Project Details

Human leukocyte antigens (HLAs) are highly polymorphic proteins that initiate immunity by presenting pathogen-derived peptides to T cells. HLA polymorphisms mostly map to the antigen-binding cleft, thereby diversifying the repertoire of self-derived and pathogen derived peptide antigens selected by different HLA allotypes. Recently, a growing number of immunologically based drug reactions have been found to be strongly associated with specific HLA alleles. In particular, HLA-B*15:02 and HLA-A*31:01 are associated with severe skin reactions caused by certain antiepileptic drugs, but little is known about the underlying mechanisms of these associations. 

Recent research has demonstrated that direct binding of the drug to the HLA molecule led to changes in the shape and chemistry of the antigen-binding cleft, thereby altering the repertoire of endogenous peptides and driving T-cell activation. This project aims to find out whether this mechanism also applies to the case of the interactions between antiepileptic drugs and these HLA alleles.

Collaborators

  • Dr Nicole Mifsud

Research Opportunities

This research project is available to PhD students to join as part of their thesis.
Please contact the Research Group Leader to discuss your options.

Research Group

Epilepsy and Precision Medicine



Faculty Research Themes

Neuroscience

School Research Themes

Neuroscience & Psychiatry



Key Contact

For further information about this research, please contact the research group leader.

Department / Centre

Medicine and Radiology

Unit / Centre

Royal Melbourne Hospital