There is however increasing evidence that CD4 + T cells also play a critical role in the control of CMV infection, reactivation and vertical transmission. So far, much importance has been placed on the role of cytotoxic T cells (CTL) in the recognition of CMV-infected cells, and the CD8 + CTL response to CMV antigens has been widely investigated using various reliable tools and methods. Several lines of evidence indicate that both humoral and cellular immunity to CMV can reduce the frequency and severity of the disease. Human cytomegalovirus (CMV) is a ß-herpesvirus that shares common biological properties with other herpesviruses, such as persistence and latency in the host. 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. 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. 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. 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. 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. Methodsĭendritic cells obtained from CMV-seropositive donors were loaded with a recombinant gB and co-cultured with autologous CD4 + T cells.

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. 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.

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