INDUCTION OF FELINE IMMUNODEFICIENCY VIRUS-SPECIFIC CYTOTOXIC T-CELLSIN-VIVO WITH CARRIER-FREE SYNTHETIC PEPTIDE

The role of cellular immunity in the establishment and progression of immunosuppressive lentivirus infection remains equivocal. To develop a model system with which these aspects of the host immune response can be studied experimentally, eve examined the responses of cats to a hy brid peptide containing predicted T- and B-cell epitopes from the gag and env genes of feline immunodeficiency virus (FIV). Cats were immuni zed with an unmodified 17-residue peptide incorporating residues 196 t o 208 (from gag capsid protein p24) and 395 to 398 (from env glycoprot ein gp120) of the FIV Glasgow-8 strain by using Quil A as an adjuvant. Virus-specific lymphocytotoxicity was measured by chromium-51 release assays. The target cells were autologous or allogeneic skin fibroblas ts either infected with recombinant FIV gag vaccinia virus or pulsed w ith FN peptides. Effector cells were either fresh peripheral blood mon onuclear cells or T-cell lines stimulated with FIV peptides in vitro. Cytotoxic effector cells from immunized cats lysed autologous, but not allogeneic, target cells when they were either infected with recombin ant FIV gag vaccinia virus or pulsed with synthetic peptides comprisin g residues 196 to 205 or 200 to 208 plus 395. Depletion of CD8(+) T ce lls, but not CD4(+) T cells, from the effector cell population abrogat ed the lymphocytotoxicity. Immunized cats developed an antibody respon se to the 17-residue peptide immunogen and to recombinant p24. However , no antibodies which recognized smaller constituent peptides could be detected. This response correlated with peptide-induced T-cell prolif eration in vitro. This study demonstrates that cytotoxic T lymphocytes specific for FIV can be induced following immunization with an unmodi fied short synthetic peptide and defines a system in which the protect ive or pathological role of such responses can be examined.