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HLA-DR and HLA-DP Restricted Epitopes from Human Cytomegalovirus Glycoprotein B Recognized by CD4(+) T-Cell Clones from Chronically Infected Individuals

PURPOSE: Helper CD4(+) T cells presumably play a major role in controlling cytomegalovirus (CMV) by providing help to specific B and CD8(+) cytotoxic T cells, as well as through cytotoxicity-mediated mechanisms. Since CMV glycoprotein B (gB) is a major candidate for a subunit vaccine against CMV, we...

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Detalles Bibliográficos
Autores principales: Ventura, Claire, Bisceglia, Hélène, Girerd-Chambaz, Yves, Burdin, Nicolas, Chaux, Pascal
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3528953/
https://www.ncbi.nlm.nih.gov/pubmed/22797815
http://dx.doi.org/10.1007/s10875-012-9732-x
Descripción
Sumario:PURPOSE: Helper CD4(+) T cells presumably play a major role in controlling cytomegalovirus (CMV) by providing help to specific B and CD8(+) cytotoxic T cells, as well as through cytotoxicity-mediated mechanisms. Since CMV glycoprotein B (gB) is a major candidate for a subunit vaccine against CMV, we searched for gB-epitopes presented by human leukocyte antigen (HLA)-class II molecules. METHODS: Dendritic cells obtained from CMV-seropositive donors were loaded with a recombinant gB and co-cultured with autologous CD4(+) T cells. Microcultures that specifically recognized gB were cloned by limiting dilution using autologous Epstein-Barr virus (EBV)-immortalized B cells pulsed with gB as antigen-presenting cells. To pinpoint precisely the region encoding the natural epitope recognized by a given CD4(+) clone, we assessed the recognition of recombinant Escherichia coli expressing gB-overlapping polypeptides after their processing by autologous EBV-B cells. RESULTS: We isolated several gB-specific CD4(+) T-cell clones directed against peptides gB(190-204), gB(396-410), gB(22-36) and gB(598-617) presented by HLA-DR7, HLA-DP10 and HLA-DP2. While their precise role in controlling CMV infection remains to be established, gB-specific CD4(+) T cells are likely to act by directly targeting infected HLA-class II cells in vivo, as suggested by their recognition of EBV-B cells infected by the Towne CMV strain. CONCLUSIONS: The characterization of such gB-epitopes presented by HLA-class II should help to understand the contribution of CD4(+) T-cell responses to CMV and may be of importance both in designing a vaccine against CMV infection and in immunomonitoring of subjects immunized with recombinant gB or with vectors encoding gB.