We investigated the specificity of the T helper (T) cell immune response to three alphaviruses: Venezuelan equine encephalomyelitis (VEE), eastern equine encephalitis (EEE) and western equine encephalitis (WEE). Single cell suspensions were prepared from spleens of virus-primed C3H mice, and T lymphocyte populations were enriched by nylon wool chromatography. T cells were incubated with irradiated, syngeneic splenic stimulator cells previously exposed to purified virus. Cellular proliferation was measured by [H]thymidine uptake 5 days post-stimulation. The predominant proliferating cell type secreted interleukin-2 and was of the T cell phenotype Thy-1, Lyt-1,2, L3T4. Stimulation of VEE, EEE and WEE virus-primed T cells with homologous and heterologous virus resulted primarily in a proliferative response specific for the immunizing virus. The corresponding antibody response, as measured by ELISA using purified virus as antigen, was also specific for the immunizing virus. The magnitude of the blastogenic response of VEE TC-83 virus-primed lymphocytes to a battery of VEE subtype viruses was remarkably similar to schemes of antigenic classification. The results indicate that the dominant T cell epitopes on these alphaviruses represent regions largely virus-specific and lead to a virus-specific B cell response which does not change over time after primary inoculations of mice with VEE and WEE viruses and multiple inoculations of mice with EEE virus.


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