Pulmonary V beta 4+ T cells from Histoplasma capsulatum-infected mice respond to a homologue of Sec31 that confers a protective response.

Abstract

The population of V beta 4+ T cells expands in the lungs of C57BL/6 mice infected with Histoplasma capsulatum, and the elimination of these cells impairs protective immunity. To determine the antigen or antigens that trigger their proliferation, V beta 4+ T cell hybridomas were generated from the lungs and spleens of infected mice. We mapped the antigenic determinants by T cell Western blot. Pulmonary and splenic T cells recognized 3 regions comprising <25, 55-70, and 125-140 kDa. The majority of hybridomas from lungs, but not from spleens, responded to the high molecular mass region. A protein from that area was identified, by amino acid sequencing, as a homologue of Sec31 from Saccharomyces cerevisiae. Vaccination with recombinant Sec31 reduced fungal burden and improved survival in mice, and its efficacy was critically dependent on the presence of V beta 4+ T cells. Thus, a homologue of Sec31 is a trigger of the expansion of the V beta 4+ T cell population and is important to the generation of protective immunity.