V beta 6+ 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 Vbeta6+; the remainder were Vbeta14+. Amino acid motifs of the CDR3 region from Vbeta6+ cells were predominantly IxGGG, IGG, or SxxGG, whereas it was uniformly SFSGG for Vbeta14+ clones. Short term T cell lines from Vbeta6+-depleted mice failed to recognize Ag, and no T cell clones could be generated. To determine whether Vbeta6+ cells were functionally important, we eliminated them during vaccination. Depletion of Vbeta6+ cells abrogated protection in vivo and upon adoptive transfer of cells into TCR alphabeta(-/-) mice. Transfer of a Vbeta6+, but not a Vbeta14+, clone into TCR alphabeta(-/-) mice prolonged survival. Cytokine generation by Ag-stimulated splenocytes from immunized mice depleted of Vbeta6+ cells was similar to that of controls. The efficacy of the Vbeta6+ clone was associated with elevated production of IFN-gamma, TNF-alpha, and GM-CSF compared with that of the Vbeta14+ clone. More Vbeta6+ cells were present in lungs and spleens of TCR alphabeta(-/-) on day 3 postinfection compared with Vbeta14+ cells. Thus, a single Vbeta family was essential for vaccine-induced immunity. Moreover, the mechanism by which Vbeta6+ contributed to protective immunity differed between unfractionated splenocytes and T cell clones.
Deepe
G S
GS
Division of Infectious Diseases, University of Cincinnati College of Medicine, and Veterans Affairs Hospital, Cincinnati, OH 45267, USA. george.deepe@uc.edu
Gibbons
R
R
D019264:Adoptive Transfer; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D018834:Chaperonin 60 / Q000276:immunology; D002999:Clone Cells / Q000637:transplantation; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis; D005657:Fungal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D006658:Histoplasma / Q000276:immunology*; D006660:Histoplasmosis / Q000276:immunology* / Q000517:prevention & control; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology; D017434:Protein Structure, Tertiary; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D013154:Spleen / Q000166:cytology / Q000637:transplantation; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism* / Q000637:transplantation
D018834:Chaperonin 60; D016207:Cytokines; D005657:Fungal Vaccines; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta