Vβ6+ T cells are obligatory for vaccine-induced immunity to Histoplasma capsulatum

We examined TCR usage to a protective fragment of heat shock protein 60 from the fungus, Histoplasma capsulatum. Nearly 90% of T cell clones from C57BL/6 mice vaccinated with this protein were V beta6(+); the remainder were V beta 14(+). Amino acid motifs of the CDR3 region from V beta6(+) cells were predominantly IxGGG, IGG, or SxxGG, whereas it was uniformly SFSGG for V beta 14(+) clones. Short term T cell lines from V beta6(+)-depleted mice failed to recognize Ag, and no T cell clones could be generated. To determine whether V beta6(+) cells were functionally important, we eliminated them during vaccination. Depletion of V beta6(+) cells abrogated protection in vivo and upon adoptive transfer of cells into TCR alpha beta (-/-) mice. Transfer of a V beta6(+), but not a V beta6(+), clone into TCR alpha beta (-/-) mice prolonged survival. Cytokine generation by Ag-stimulated splenocytes from immunized mice depleted of V beta6(+) cells was similar to that of controls. The efficacy of the V beta6(+) clone was associated with elevated production of IFN-gamma, TNF-alpha, and GM-CSF compared with that of the V beta 14(+) clone. More V beta6(+) cells were present in lungs and spleens of TCR a13' on day 3 postinfection compared with V beta 14(+) cells. Thus, a single V beta family was essential for vaccine-induced immunity. Moreover, the mechanism by which V beta6(+) contributed to protective immunity differed between unfractionated splenocytes and T cell clones.