The protective immune response to heat shock protein 60 of Histoplasma capsulatum is mediated by a subset of V beta 8.1/8.2+ T cells.
Immunization with recombinant heat shock protein 60 (rHsp60) from Histoplasma capsulatum or a region of the protein designated fragment 3 (F3) confers protection from a subsequent challenge in mice. To determine the T cell repertoire involved in the response to Hsp60, T cell clones from C57BL/6 mice immunized with rHsp60 were generated and examined for Vbeta usage by flow cytometry and RT-PCR. Vbeta8.1/8.2(+) T cells were preferentially expanded; other clones bore Vbeta4, -6, or -11. When Vbeta8.1/8.2(+) cells were depleted in mice, Vbeta4(+) T cell clones were almost exclusively isolated. Measurement of cytokine production demonstrated that nine of 16 Vbeta8.1/8.2(+) clones were Th1, while only three of 13 non-Vbeta8.1/8.2(+) clones were Th1. In mice immunized with rHsp60, depletion of Vbeta8.1/8.2(+), but not Vbeta6(+) plus Vbeta7(+), T cells completely abolished the protective efficacy of Hsp60 to lethal and sublethal challenges. Examination of the TCR revealed that a subset of Vbeta8.1/2(+) clones that produced IFN-gamma and were reactive to F3 shared a common CDR3 sequence, DGGQG. Transfer of these T cell clones into TCR alpha/beta(-/-) or IFN-gamma(-/-) mice significantly improved survival, while transfer of other Vbeta8.1/8.2(+) clones that were F3 reactive but were Th2 or clones that were not reactive to F3 but were Th1 did not confer protection. These data indicate that a distinct subset of Vbeta8.1/8.2(+) T cells is crucial for the generation of a protective response to rHsp60.
Scheckelhoff
Mark
M
Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
Deepe
George S
GS
D000818:Animals; D002460:Cell Line; D018834:Chaperonin 60 / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D002999:Clone Cells / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000637:transplantation; D016207:Cytokines / Q000096:biosynthesis; D005657:Fungal Vaccines / Q000008:administration & dosage / Q000276:immunology; D006658:Histoplasma / Q000235:genetics / Q000276:immunology*; D006660:Histoplasmosis / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D007135:Immunoglobulin Variable Region / Q000032:analysis / Q000096:biosynthesis; D016219:Immunotherapy, Adoptive / Q000379:methods; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008819:Mice, Nude; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000008:administration & dosage / Q000096:biosynthesis* / Q000172:deficiency / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology / Q000637:transplantation; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology
D018834:Chaperonin 60; D016207:Cytokines; D005657:Fungal Vaccines; D007135:Immunoglobulin Variable Region; D016693:Receptors, Antigen, T-Cell, alpha-beta; C113249:T cell receptor peptide Vbeta8.1; D014614:Vaccines, Synthetic