期刊
PLOS ONE
卷 9, 期 4, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0095339
关键词
-
资金
- Swiss National Science Foundation (SNF) [310030-129828-1]
- Swiss Center for Applied Human Toxicology (SCAHT)
- Swiss National Science Foundation (SNF) [310030_129828] Funding Source: Swiss National Science Foundation (SNF)
Abacavir hypersensitivity is a severe hypersensitivity reaction which occurs exclusively in carriers of the HLA-B*57:01 allele. In vitro culture of PBMC with abacavir results in the outgrowth of abacavir-reacting CD8(+) T cells, which release IFN gamma and are cytotoxic. How this immune response is induced and what is recognized by these T cells is still a matter of debate. We analyzed the conditions required to develop an abacavir-dependent T cell response in vitro. The abacavir reactivity was independent of co-stimulatory signals, as neither DC maturation nor release of inflammatory cytokines were observed upon abacavir exposure. Abacavir induced T cells arose in the absence of professional APC and stemmed from naive and memory compartments. These features are reminiscent of allo-reactivity. 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. 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%. 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据