T-cell-mediated drug hypersensitivity: immune mechanisms and their clinical relevance
10.5415/apallergy.2016.6.2.77
- Author:
James YUN
1
;
Fenfen CAI
;
Frederick J LEE
;
Werner J PICHLER
Author Information
1. Department of Clinical Immunology and Allergy, Royal North Shore Hospital, St Leonards, NSW 2065, Australia. James.Yun@health.nsw.gov.au
- Publication Type:Review
- Keywords:
Drug hypersensitivity;
Receptors, antigen, T-Cell;
Haptens;
HLA antigens
- MeSH:
Binding Sites;
Classification;
Drug Hypersensitivity;
Drug-Related Side Effects and Adverse Reactions;
Hand;
Haptens;
HLA Antigens;
Major Histocompatibility Complex;
Receptors, Antigen, T-Cell;
T-Lymphocytes
- From:
Asia Pacific Allergy
2016;6(2):77-89
- CountryRepublic of Korea
- Language:English
-
Abstract:
T-cell-mediated drug hypersensitivity represents a significant proportion of immune mediated drug hypersensitivity reactions. In the recent years, there has been an increase in understanding the immune mechanisms behind T-cell-mediated drug hypersensitivity. According to hapten mechanism, drug specific T-cell response is stimulated by drug-protein conjugate presented on major histocompatibility complex (MHC) as it is presented as a new antigenic determinant. On the other hand, p-i concept suggests that a drug can stimulate T cells via noncovalent direct interaction with T-cell receptor and/or peptide-MHC. The drug binding site is quite variable and this leads to several different mechanisms within p-i concept. Altered peptide repertoire can be regarded as an 'atypical' subset of p-i concept since the mode of the drug binding and the binding site are essentially identical to p-i concept. However, the intracellular binding of abacavir to HLA-B*57:01 additionally results in alteration in peptide repertoire. Furthermore the T-cell response to altered peptide repertoire model is only shown for abacavir and HLA-B*57:01 and therefore it may not be generalised to other drug hypersensitivity. Danger hypothesis has been postulated to play an important role in drug hypersensitivity by providing signal 2 but its experimental data is lacking at this point in time. Furthermore, the recently described allo-immune response suggests that danger signal may be unnecessary. Finally, in view of these new understanding, the classification and the definition of type B adverse drug reaction should be revised.
