B-cell activation in vitro by helper T cells specific to a protein region that is recognized both by T cells and by antibodies

This laboratory had previously mapped the regions of T and B cell recognition on sperm whale myoglobin (Mb). Mb has five regions (E1-E5) that are recognized by both T cells and B cells (i.e. antibodies, Abs) and an additional region (E6) that is recognized exclusively by T cells (i.e., T-E6) and to which no Abs are detectable. The responses to the site are each under separate genetic control. Recently, we showed in an H-2(d) haplotype that T-E6 cells preferentially activated Mb-primed B cells (B-Mb) that made Abs against sites within E3 and E4 on the same protein. In the present work, we established, from Mb-primed SJL mice, an E4-specific T cell line (T-E4) by passage in vitro with synthetic peptide E4. At relatively low numbers, these T cells activated syngeneic B-Mb cells in vitro to produce anti-Mb Abs that recognized each of the antigenic sites within regions El, E2, E3, E4 and E5. We confirmed the ability of T-E4 to activate B cells that produce Abs against each of these regions by allowing T-E4 to activate in vitro syngeneic B cells that had been primed with El, E2, E3, E4 or E5. The helper activity of T-E4 cells was dependent on the in vitro concentration of the challenge Ag (intact Mb or peptide E4). Thus, T cells against an epitope may provide help restricted to B cells that make Abs against selected antigenic sites or they may activate B cells that make Abs against all the antigenic sites of a protein. This might depend on the site-specificity of the T cell and/or on the host.