IAI Accepts, published online ahead of print on 2 November 2009

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Infect. Immun. doi:10.1128/IAI.00994-09
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Discordant Brucella melitensis Antigens Yield Cognate CD8⁺ T cells in vivo

Marina Durward, Jerome Harms, Diogo Magnani, Linda Eskra, and Gary A. Splitter^*

Dept. of Pathology and Laboratory Medicine, School of Medicine and Public Health, University of Wisconsin- Madison, Madison, WI 53706; Dept. of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53706

^* To whom correspondence should be addressed. Email: splitter{at}svm.vetmed.wisc.edu.

Brucella spp. are intracellular bacteria that cause the most frequent zoonosis in the world. Though recent work has advanced the field of Brucella vaccine development, there remains no safe human vaccine. In order to produce a safe and effective human vaccine, the immune response to Brucella spp. requires greater understanding. Induction of Brucella specific CD8⁺ T cells is considered an important aspect of the host response; however, the CD8⁺ T cell response is not clearly defined. Discovering the epitope containing antigens recognized by Brucella specific CD8⁺ T cells and correlating them with microarray data will aid in determining proteins critical for vaccine development that cover a kinetic continuum during infection. Developing tools to take advantage of the BALB/c mouse model of Brucella melitensis infection will help to clarify the correlates of immunity and improve the efficacy of this model. Two H-2^d CD8⁺ T cell epitopes have been characterized, and a group of immunogenic proteins have provoked IFN- production by CD8⁺ T cells. RYCINSASL and NGSSSMATV induced cognate CD8⁺ T cells after peptide immunization that showed specific killing in vivo. Importantly, we found by microarray analysis that the genes encoding these epitopes are differentially expressed following macrophage infection, further emphasizing that these discordant genes may play an important role in the pathogenesis of Brucella melitensis infection.