Human Leukocyte Antigen (HLA) part 96

HLA and sensitivity

Allergic drug reactions occur when a drug, usually a low molecular weight molecule, has the ability to stimulate an immune response. Several alternative mechanisms of immune recognition have been proposed to explain HLA-associated  drug hypersensitivity. These mechanisms include the hapten (or pro-hapten) concept, which states that drugs and their metabolites are too small to be immunogenic on their own, but act as haptens to modify certain self-proteins in the host that lead to immune recognition of the resulting hapten: self-peptide complexes as de novo antigens. The super antigen interaction concept states that drugs  may bridge T cell receptor and HLA molecules without binding directly to peptide antigen. The p-i concept  (short for pharmacological interaction with immune receptors) states that drugs can induce the formation of HLA-drug complexes that can activate T-cell immune responses directly  without requiring a specific peptide ligand. Recently, several groups  reported data suggested that these commonly considered mechanisms mentioned above may not apply in the case of abacavir. Instead, abacavir seems to alter the peptide repertoire presented by HLA-B*57:01 by occupying sites within the antigen-binding cleft. The polymorphic residues implicated in drug interactions suggest that different drugs may bind HLA molecules or other elements of the trimolecules complex (HLA, peptide and T cell receptor) in alternative binding modes.