In search of a virotope: Identification of herpesvirus specific CD8T cells
Redwood, A., Jing, L., Tran, T., White, K., Mallal, S., Koelle, D. and Phillips, E. (2015) In search of a virotope: Identification of herpesvirus specific CD8T cells. In: Science on the Swan, 21 - 23 April 2015, Perth, Western Australia.
Immunologically-mediated adverse drug reactions (IMADRs) cause significant economic burden, and patient morbidity and mortality. Many severe T-cell mediated reactions are restricted by class I and/or II HLA alleles. The rapid onset and tissue specificity of some IM-ADRs is indicative of resident effect or memory T-cell involvement, perhaps specific for persistent pathogens such as herpes simplex virus(HSV). In collaboration with others we have shown that hypersensitivity to the drug abacavir is mediated by alterations to the repertoire of self-peptide bound to HLA-B*57:01. To explain the immunopathogenesis, short latency, in complete positive predictive value of HLA risk alleles and tissue specificity of reactions such as carbamazepine(CBZ) induced Stevens-Johnson-syndrome/toxic epidermal necrolysis (SJS/TEN) associated with HLA-B*15:02, we propose a“heterologous immunity/altered peptide model” that requires the identification of the HLA-B*15:02 restricted virotope (foreign peptide) as the first step to identifying cross-reactivity with self-peptide in the presence of CBZ.
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|Murdoch Affiliation:||Institute for Immunology and Infectious Diseases|
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