Yersinia pestisV Protein Epitopes Recognized by CD4 T Cells

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Abstract
Pneumonic plague, an often-fatal disease for which no vaccine is presently available, results from pulmonary infection by the bacteriumYersinia pestis. TheY. pestisV protein is a promising vaccine candidate, as V protein immunizations confer to mice significant protection against aerosolizedY. pestis. CD4 T cells play central roles during vaccine-primed immune responses, but their functional contributions toY. pestisvaccines have yet to be evaluated and optimized. Toward that end, we report here the identification of three distinct epitopes within theY. pestisV protein that activate CD4 T cells in C57BL/6 mice. To our knowledge, these are the first identified CD4 T-cell epitopes in anyY. pestisprotein. The epitopes are restricted by the I-Abclass II major histocompatibility complex molecule and are fully conserved betweenY. pestis,Yersinia pseudotuberculosis, andYersinia enterocolitica. Immunizing mice with a V protein-containing vaccine or with short peptides containing the identified epitopes primes antigen-specific production of interleukin 2 and gamma interferon by CD4 T cells upon their restimulation in vitro. Consistent with prior studies documenting protective roles for CD4 T cells duringY. enterocoliticainfection, vaccinating mice with a 16-amino-acid peptide encoding one of the epitopes suffices to protect against an otherwise lethalY. enterocoliticachallenge. The identification of these epitopes will permit quantitative assessments of V-specific CD4 T cells, thereby enabling researchers to evaluate and optimize the contribution of these cells to vaccine-primed protection against pneumonic plague.