Characteristics of the Strong Antibody Response to Mycobacterial Hsp70: A Primary, T Cell-Dependent IgG Response with no Evidence of Natural Priming or γδ T Cell Involvement

Abstract

AbstractDespite its high degree of evolutionary conservation, hsp70 is a surprisingly robust Ag, to such a degree that it is under consideration as a potential substrate in vaccine development. The cellular basis of the strong humoral response, however, is unknown, although it is often hypothesized to derive from restimulation of memory T cells that have been primed by hsp of intestinal flora. In this study, we tested this hypothesis and performed additional studies on the immune response to hsp70 of Mycobacterium tuberculosis. Superficially, the primary Ab response to this protein resembles a T cell-dependent secondary one, constituted almost exclusively by IgG. However, there is no evidence of natural priming, as revealed both by in vitro stimulation experiments and by immunity in germfree mice. Although hsp70 stimulates γδ and αβ T cells from unprimed mice to proliferate in vitro, γδ cells are not required for the strong humoral response, which is indistinguishable in normal and γδ T cell-deficient mice. Thus, the unusual immunogenicity of this protein in eliciting a humoral response appears to be due to a strong αβ T cell response with no evidence of natural priming or a γδ T cell involvement.