Activation of the TCR complex by peptide-MHC and superantigens.
Drug hypersensitivity reactions are immune mediated, with T lymphocytes being stimulated by the drugs via their T-cell antigen receptor (TCR). In the nonpathogenic state, the TCR is activated by foreign peptides presented by major histocompatibility complex molecules (pMHC). Foreign pMHC binds with sufficient affinity to TCRαβ and thereby elicits phosphorylation of the cytoplasmic tails of the TCRαβ-associated CD3 subunits. The process is called TCR triggering. In this review, we discuss the current models of TCR triggering and which drug properties are crucial for TCR stimulation. The underlying molecular mechanisms mostly include pMHC-induced exposure of the CD3 cytoplasmic tails or alterations of the kinase-phosphatase equilibrium in the vicinity of CD3. In this review, we also discuss triggering of the TCR by small chemical compounds in context of these general mechanisms.
Department of Molecular Immunology, Institute for Biology III, Faculty of Biology, BIOSS Center for Biological Signalling Studies, Centre for Chronic Immunodeficiency CCI, University of Freiburg and Max Planck-Institute of Immunobiology and Epigenetics, Freiburg, Germany.
Christine
C
Louis-Dit-Sully
Britta
B
Blumenthal
Marlena
M
Duchniewicz
Katharina
K
Beck-Garcia
Gina J
GJ
Fiala
Esmeralda
E
Beck-García
Markus
M
Mukenhirn
Susana
S
Minguet
Wolfgang W A
WW
Schamel
D000818:Animals; D006649:Histocompatibility Antigens / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000276:immunology*; D018089:Superantigens / Q000276:immunology*
D006649:Histocompatibility Antigens; D000949:Histocompatibility Antigens Class II; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D018089:Superantigens