INTERSITE HELPER FUNCTION OF T-CELLS SPECIFIC FOR A PROTEIN EPITOPE THAT IS NOT RECOGNIZED BY ANTIBODIES

Humoral responses to a protein require T-B cell communication for B ce ll activation by T cells. Previous studies from this laboratory have m apped the T and B cell recognition sites (epitopes) on sperm-whale myo globin (Mb) and several other proteins. It was found that, five of six regions on Mb recognized by T cells are also recognized by B cells (i .e. antibodies). There is, however, one region (E6) residing within Mb residues 61-77, that is recognized only by T cells and to which no an tibody (Ab) responses are detectable. To investigate the function of t his exclusive T cell epitope, we established, from E6-primed BALB/c mi ce, an E6-specific T cell line (T-E6) which comprised Th2-type cells. These T cells provided help in vitro to B cells from Mb-primed BALB/c mice and activated them to produce anti-Mb Abs of the IgM (58.2%) and IgG (41.8%) isotypes. The helper activity of T-B6 cells was dependent on the concentration of the challenging Ag (intact Mb or peptide E6) i n culture. Action of soluble factors released from E6-activated T-E6 c ells on B-Mb cells led to low production of anti-Mb Abs, suggesting th at activation of the B cells was more dependent on their contact with T cells. Mapping of the epitope recognition of the anti-Mb Abs produce d in vitro by B-Mb cells on activation by T-E6 revealed that this acti vation was not general to all antigenic regions recognized by anti-Mb Abs in BALB/c mice. E6-specific T cells caused in vitro activation and differentiation of B-Mb cells into plasma cells that secreted anti-Mb Abs directed, in decreasing order, against the following Mb regions: E4 (107-120) > E3 (87-100) > E1 (10-22). Little or no Ab responses cou ld be detected against peptides E2 (50-62), E5 (141-153) and E6 (61-77 ). With B cells of peptide-primed BALB/c mice, T, cells activated stro ngly E4-, E3- or E1-, and only very slightly E2- or E6-, primed B cell s to secrete Abs against the correlate peptide, but failed completely to activate E5-primed B cells. The results show that a protein T cell epitope, to which no Abs are detectable, plays an active role in B cel l responses against other epitopes within the same protein.