Frequent recognition of BCRF1, a late lytic cycle protein of Epstein-Barr virus, in the HLA-B*2705 context: evidence for a TAP-independent processing.
Using a transient COS transfection assay, allowing a rapid estimation of the dominant CD8(+) T cell responses against a large number of HLA/viral protein combinations within polyclonal cell lines, we searched for HLA-B*2705-restricted CD8 T cell responses to Epstein-Barr virus (EBV) within T cell samples enriched for EBV-reactive cells. Among the 18 EBV proteins tested, only 2, the latent protein EBNA3A and the late lytic protein BCRF1 (viral IL-10), appeared dominant in the B27 context, as they triggered significant TNF and cytolytic responses in some donors. We provide evidence that the B27/BCRF1 epitope (RRLVVTLQC) is located in the signal sequence and that it can be presented in a TAP-independent manner. Using B27/BCRF1 monomeric complexes coated on immunomagnetic beads, we sorted out BCRF1-specific CD8 T cells from 8 of 15 HLA-B27(+) donors. This is, to our knowledge, the first demonstration of a recognition of BCRF1, suggesting that some immune control against EBV exists even during the late stage of the lytic cycle. This result also strengthens the unusual ability of HLA-B*2705 to present peptide in a TAP-independent manner.
INSERM U463, Institut de Biologie, Nantes, France.
X
X
Saulquin
M
M
Bodinier
M A
MA
Peyrat
A
A
Hislop
E
E
Scotet
F
F
Lang
M
M
Bonneville
E
E
Houssaint
D000818:Animals; D017951:Antigen Presentation; D019556:COS Cells; D002460:Cell Line; D003601:Cytotoxicity Tests, Immunologic; D000939:Epitopes / Q000276:immunology; D015796:HLA-B27 Antigen / Q000235:genetics / Q000276:immunology*; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation; D029543:Nucleocytoplasmic Transport Proteins; D010455:Peptides / Q000276:immunology; D011506:Proteins / Q000502:physiology*; D016601:RNA-Binding Proteins; D013583:Synovial Membrane / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology*
C066460:BCRF1 protein, Human herpesvirus 4; D000939:Epitopes; D015796:HLA-B27 Antigen; C122111:NXF1 protein, human; D029543:Nucleocytoplasmic Transport Proteins; D010455:Peptides; D011506:Proteins; D016601:RNA-Binding Proteins; D014764:Viral Proteins; D016753:Interleukin-10