Poster Presentation 23rd Annual Lorne Proteomics Symposium 2018

Identification of T cell epitopes involved in adverse reactions to β-lactam antibiotics (#142)

Patricia Illing 1 , Shawn Goh 1 , Nicole Mifsud 1 , Robert Puy 2 , Robyn O'Hehir 2 , Anthony Purcell 1
  1. Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia
  2. Allergy, Immunology and Respiratory Medicine, Monash University, The Alfred Hospital, Prahran, Victoria, Australia

Although widely used, penicillins cause a range of adverse drug reactions ranging from cutaneous reactions to anaphylaxis in 1-10% of individuals treated. These reactions are generally classified as idiosyncratic and involve inappropriate activation of the immune system during drug administration. Depending on reaction phenotype, a range of immune cell types have been implicated, including both CD4 and CD8 T cells. In healthy individuals, CD8 and CD4 T cells are normally activated via the presentation of pathogen derived peptides on the surface of antigen presenting cells by MHC class I and II molecules respectively. In contrast, self-derived peptides presented by the MHC are usually ignored. The ability of β-lactam antibiotics, including penicillins, to covalently modify proteins is well established, and the prevailing hypothesis for T cell activation in adverse reactions to penicillins is the presentation of immunogenic penicillin-modified self-peptides by MHC molecules. We have recruited a cohort of penicillin allergic patients from The Alfred Hospital Allergy Clinic (n=10), who have experienced a range of adverse reactions to penicillins including amoxicillin. In preliminary studies we have isolated drug responsive T cells from a patient who experienced an accelerated response to amoxicillin that are activated via the MHC class I molecule HLA-A*02:01. Using a B-lymphoblastoid cell line derived from this patient, we are exploring the peptides presented by HLA-A*02:01 of untreated and drug treated cells via an immunoaffinity purification, LC-MS/MS workflow.  Evidence for drug haptenated peptides will be discussed. These analyses will form the foundation of a broader characterisation of potential drug-induced T cell epitopes across the patient cohort.