Antigen-specific CD4+ T cells recognize epitopes of protective antigen following vaccination with an anthrax vaccine

Detection of antigen-specific CD4+ T cells is facilitated by the use of fluorescently labeled soluble peptide-major histocompatibility complex (MHC) multimers which mirror the antigen specificity of T-cell receptor recognition. We have used soluble peptide-MHC class II tetramers containing peptides from the protective antigen (PA) of Bacillus anthracis to detect circulating T cells in peripheral blood of subjects vaccinated with an anthrax vaccine. PA-specific HLA class II-restricted T lymphocytes were isolated which displayed both TH1- and TH2-like characteristics, indicating heterogeneity of the lymphocyte lineage within the CD4+ response. Presentation of antigen to these T-cell clones by HLA-matched antigen-presenting cells exposed to the intact PA protein confirmed that the identified epitopes are indeed naturally processed by the human immune system. Specific tetramer-derived T-cell profiling may be useful for monitoring helper CD4+ T-cell responses to anthrax vaccination.