Mapping of T helper cell epitopes by using peptides spanning the 19-kDa protein of Mycobacterium tuberculosis. Evidence for unique and shared epitopes in the stimulation of antibody and delayed-type hypersensitivity responses.

Abstract

In vivo and in vitro T cell responses to overlapping 20-mer peptides that span the entire 19-kDa protein of Mycobacterium tuberculosis have been compared in three different strains of mice. Immunization of the mice with peptides and analysis of specific antibody production is an in vivo assay of Th cell activity. Peptides 1-20 and 61-80 elicited strong IgG1 responses in BALB/cJ, C57BL/10J, and B10.BR mice, indicating that these peptides could stimulate Th cells, possibly of a Th2 phenotype. T cells isolated from peptide-immunized mice were challenged in vitro with peptide, and their proliferative responses were analyzed. T cells from these three strains of mice immunized with peptides 1-20, 61-80, and 76-95 also responded to challenge with specific peptide in vitro. In addition, B10.BR mice and BALB/cJ mice showed antibody and T cell proliferative responses to peptides 136-155 and 145-159, respectively. Thus, in vitro proliferating T cells were found to possess specificities for peptide epitopes that were almost identical to those of the antibody-producing cells. Delayed-type hypersensitivity (DTH) responses to these peptides were also examined in the three strains. Interestingly, the T cells responding in the DTH assay had Ag specificities that were quite different from those identified in the antibody and proliferation assays. These results suggested that DTH Th cells form a separate population from antibody Th and proliferative T cells and these populations of cells were differentially activated, in an Ag-specific manner.