Defining the mechanism(s) of protection by cytolytic CD8 T cells against a cryptic epitope derived from a retroviral alternative reading frame.
The biological significance of protective CD8 T-cell-mediated responses against non-traditional alternative reading frame epitopes remains relatively unknown. Cytolytic CD8 T cells (CTL) specific for a non-traditional cryptic MHC class I epitope, SYNTGRFPPL, are critically involved in the protection of mice during infection with the LP-BM5 murine retrovirus. The goal of this study was to determine the functional properties of the protective SYNTGRFPPL-specific CTL during LP-BM5 infection of susceptible BALB/c CD8(-/-) mice. Direct infection experiments and adoptive transfer of CD8 T cells derived from perforin (pfp)(-/-), IFN gamma(-/-), FasL(-/-) and, as a positive control, wild-type BALB/c mice, were utilized to assess the effector mechanisms responsible for protection. Our results indicate that SYNTGRFPPL-specific effector CTL preferentially utilize perforin-mediated cytolysis to provide protection against LP-BM5-induced pathogenesis, whereas CTL production of IFN gamma is not required. Our results also suggest a minimal contribution of FasL/Fas-mediated lysis during the effector response. Collectively, these results provide insight into effector mechanisms utilized by protective CTL directed against non-traditional cryptic epitopes during disease protection.
Rutkowski
Melanie R
MR
Department of Microbiology and Immunology, Dartmouth Medical School, Lebanon, NH, USA.
Ho
On
O
Green
William R
WR
D019264:Adoptive Transfer; D000818:Animals; D000956:Antigens, Viral / Q000235:genetics* / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003601:Cytotoxicity Tests, Immunologic; D000939:Epitopes / Q000276:immunology*; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D054353:Perforin / Q000276:immunology; D016364:Reading Frames; D012190:Retroviridae / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000956:Antigens, Viral; D000939:Epitopes; D054353:Perforin