|
KMID : 1143120160060020077
|
|
Asia Pacific Allergy
2016 Volume.6 No. 2 p.77 ~ p.89
|
|
|
T-cell-mediated drug hypersensitivity: immune mechanisms and their clinical relevance
|
|
Yun James
Cai Fenfen
Lee Frederick J
Pichler Werner J
|
|
|
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.
|
|
|
KEYWORD
|
|
|
Drug hypersensitivity, Receptors, antigen, T-Cell, Haptens, HLA antigens
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
|