MHC-lb restricted T cell responses against Listeria monocytogenes

Grants and Contracts Details


Listeria monocytogenes (Lm) is a category B priority pathogen that causes outbreaks of foodborne illness with a high incidence of morbidity and mortality. To achieve sterilizing immunity against Lm, CD8~ I cells must recognize antigens bound to MHC-l proteins on the surface of infected cells, an event that results in activation of the T cells and acquisition of protective effector functions. Classical MHC-l proteins (MHC-la) have been studied for decades, however, comparatively little is known about most of the non-classical MHC-l proteins (MHC-lb). We developed a ME-IC-la deficient mouse model of Lm infection to study the role of MHC-lb restricted I cells in the clearance of intracellular bacterial pathogens. Our central hypothesis is that Lm-immune mice contain memory CD8t T cells that recognize novel MHC-lb proteins, and that these T cells play a significant role in the clearance of secondary Lm infection. In preliminary studies, we showed that CD8t T cells that recognize antigen in the context of a novel (not M3) MHC-lb protein are activated during Lm infection. We have identified nine murine MHC-lb genes as likely candidates to express proteins that could serve as antigen presenting molecules during infection. In this application, we propose to: 1) develop a panel of human macrophage-like cells transfected with each of the nine candidate MHC-Ib genes and 2) use the MHC-lb transfectants to determine how many different MHC-Ib proteins are capable of presenting antigen to T cells during Lm infection. These studies will help to define the role of MHC-lb restricted T cells in protective immune responses against Lm and may facilitate the identification of new classes of antigens for all intracellular bacterial pathogens. Since most MHC-Ib proteins are non-polymorphic, antigens that bind to MHC-lb proteins are likely to be recognized by most, if not all of the individuals in a given population. This makes ME-IC-lb antigens particularly attractive candidates for inclusion in vaccines designed to protect against infection with intracellular bacterial pathogens.
Effective start/end date6/18/095/31/12


  • National Institute of Allergy and Infectious Diseases: $147,758.00


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