Pulmonary V beta 4+ T cells from Histoplasma capsulatum-infected mice respond to a homologue of Sec31 that confers a protective response.
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.
Division of Infectious Diseases, Department of Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0560, USA.
Mark R
MR
Scheckelhoff
George S
GS
Deepe
D000818:Animals; D002352:Carrier Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D006658:Histoplasma / Q000187:drug effects* / Q000235:genetics / Q000276:immunology*; D006660:Histoplasmosis / Q000276:immunology* / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D010750:Phosphoproteins / Q000008:administration & dosage / Q000494:pharmacology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D033921:Vesicular Transport Proteins
D002352:Carrier Proteins; D010750:Phosphoproteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; C106113:SEC31 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D033921:Vesicular Transport Proteins