Allotype specific interactions of drugs and HLA molecules in hypersensitivity reactions
Current Opinion in Immunology, 2016•Elsevier
Highlights•Studies of HLA/ADR associations suggest diverse modes of HLA–drug
interaction.•Non-covalent interactions with HLA-peptide appear highly allotype
specific.•Hapten responses may be less restricted due to peptide mediated HLA
interactions.•T cell diversity may provide information about the mode of HLA–drug
interaction.It is hypothesised that associations between adverse drug reactions and specific
alleles of the human leukocyte antigens arise due to specific interactions between the …
interaction.•Non-covalent interactions with HLA-peptide appear highly allotype
specific.•Hapten responses may be less restricted due to peptide mediated HLA
interactions.•T cell diversity may provide information about the mode of HLA–drug
interaction.It is hypothesised that associations between adverse drug reactions and specific
alleles of the human leukocyte antigens arise due to specific interactions between the …
Highlights
- Studies of HLA/ADR associations suggest diverse modes of HLA–drug interaction.
- Non-covalent interactions with HLA-peptide appear highly allotype specific.
- Hapten responses may be less restricted due to peptide mediated HLA interactions.
- T cell diversity may provide information about the mode of HLA–drug interaction.
It is hypothesised that associations between adverse drug reactions and specific alleles of the human leukocyte antigens arise due to specific interactions between the human leukocyte antigen molecules and the causative drug that stimulate immune responses targeting drug exposed tissues. To date this has only been definitively demonstrated for abacavir, an antiretroviral that causes a systemic adverse drug reaction, abacavir hypersensitivity syndrome, solely in HLA-B* 57: 01+ individuals. Whilst this has informed the modification of abacavir to remove immunogenicity, there remains an imperative to define other interactions between drugs and specific HLA in order to understand the scope of interactions that can drive T cell mediated drug hypersensitivity. Here we review the current state of understanding of these interactions.
Elsevier