Immune self-reactivity triggered by carbamazepine-modified HLA-peptide repertoire
Group LeaderProfessor Patrick Kwan
T: +61 3 9342 7722
Location: Royal Melbourne Hospital
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.
- Dr Nicole Mifsud
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.