Abacavir induced T cell reactivity from drug naïve individuals shares features of allo-immune responses.

Adam, Jacqueline; Wuillemin, Natascha Andrea; Watkins, Stephan Lloyd; Jamin, Heidi; Eriksson, Klara Kristin; Villiger, Peter; Fontana, Stefano; Pichler, Werner Joseph; Yerly, Daniel (2014). Abacavir induced T cell reactivity from drug naïve individuals shares features of allo-immune responses. PLoS ONE, 9(4), e95339. Public Library of Science 10.1371/journal.pone.0095339

Preview

Text http___www.plosone.org_article_fetchObject.action_uri=info_doi_10.1371_journal.pone.0095339&representation=PDF.pdf - Published Version Available under License Creative Commons: Attribution (CC-BY). Download (2MB) | Preview

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 IFNγ 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 naïve 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.

Interest & Impact

Downloads

134 since deposited on 06 Mar 2015
13 in the past 12 months

Citations

5 Citations in Web of Science ®
6 Citations in Scopus

Search

in Google Scholar™

Services

Actions (login required)

Edit item

Actions (login required)

Edit item