How such small molecules are able to induce an immune response is not understood yet. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ĭompeting interests: The authors have declared that no competing interests exist.ĭelayed type hypersensitivity reactions (HR) to drugs are mediated by the adaptive immune system. 310030-129828-1) and by the Swiss Center for Applied Human Toxicology (SCAHT). This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.įunding: This work was supported by the Swiss National Science Foundation (SNF grant Nr. Received: JanuAccepted: MaPublished: April 21, 2014Ĭopyright: © 2014 Adam et al. PLoS ONE 9(4):Įditor: Derya Unutmaz, New York University, United States of America (2014) Abacavir Induced T Cell Reactivity from Drug Naïve Individuals Shares Features of Allo-Immune Responses. In conclusion, abacavir can alter the HLA-B*57∶01-peptide complex in a way that mimics an allo-allele (‘altered self-allele’) and create the potential for robust T cell responses.Ĭitation: Adam J, Wuillemin N, Watkins S, Jamin H, Eriksson KK, Villiger P, et al. The addition of peptides which can bind to the HLA-B*57∶01-abacavir complex and to HLA-B*58∶01 during the induction phase increased the proportion of HLA-B*58∶01 allo-reactive T cell clones from 5% to 42%. Screening for allo-reactivity revealed that about 5% of generated T cell clones (n = 136) from three donors were allo-reactive exclusively to the related HLA-B*58∶01. These features are reminiscent of allo-reactivity.
#Risk probability and impact definitions professional
Abacavir induced T cells arose in the absence of professional APC and stemmed from naïve and memory compartments. The abacavir reactivity was independent of co-stimulatory signals, as neither DC maturation nor release of inflammatory cytokines were observed upon abacavir exposure. We analyzed the conditions required to develop an abacavir-dependent T cell response in vitro. How this immune response is induced and what is recognized by these T cells is still a matter of debate.
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In vitro culture of PBMC with abacavir results in the outgrowth of abacavir-reacting CD8 + T cells, which release IFNγ and are cytotoxic. Abacavir hypersensitivity is a severe hypersensitivity reaction which occurs exclusively in carriers of the HLA-B*57∶01 allele.