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PLoS One. 2014 Apr 21;9(4):e95339. doi: 10.1371/journal.pone.0095339. eCollection 2014.

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

Author information

1
Clinic for Rheumatology and Clinical Immunology/Allergology, University Hospital of Bern, Bern, Switzerland.
2
Regional Blood Transfusion Service of the Swiss Red Cross, Bern, Switzerland.

Abstract

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.

PMID:
24751900
PMCID:
PMC3994040
DOI:
10.1371/journal.pone.0095339
[Indexed for MEDLINE]
Free PMC Article

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