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• W1895014795 startingPage "1706" @default.
• W1895014795 abstract "The antiretroviral drug abacavir (abc) elicits severe drug hypersensitivity reactions in HLA ‐ B *5701 + individuals. To understand the abc‐specific activation of CD 8 + T cells, we generated abc‐specific T ‐cell clones (abc‐ TCC s). Abc reactivity could not be linked to the metabolism and/or processing of the drug, since abc metabolizing enzymes were not expressed in immune cells and inhibition of the proteasome in APC s did not affect TCC reactivity. Ca 2+ influx assays revealed different reactivity patterns of abc‐ TCC s. While all TCC s reacted to abc presented on HLA ‐ B *5701 molecules, a minority also reacted immediately to abc in solution. Titration experiments showed that the ability to react immediately to abc correlated significantly with the TCR avidity of the T cells. Modifications of soluble abc concentrations revealed that the reactivity patterns of abc‐ TCC s were not fixed but dynamic. When TCC s with an intermediate TCR avidity were stimulated with increasing abc concentrations, they showed an accelerated activation kinetic. Thus, they reacted immediately to the drug, similar to the reaction of TCC s of high avidity. The observed immediate activation and the noninvolvement of the proteasome suggest that, in contrast to haptens, abc‐specific T ‐cell stimulation does not require the formation of covalent bonds to produce a neo‐antigenic determinant." @default.
• W1895014795 created "2016-06-24" @default.
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• W1895014795 date "2012-06-14" @default.
• W1895014795 modified "2023-10-18" @default.
• W1895014795 title "Avidity determines T-cell reactivity in abacavir hypersensitivity" @default.
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• W1895014795 doi "https://doi.org/10.1002/eji.201142159" @default.
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• W1895014795 hasPublicationYear "2012" @default.
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