Grants and Contracts Details
Description
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.
Status | Finished |
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Effective start/end date | 6/18/09 → 5/31/12 |
Funding
- National Institute of Allergy and Infectious Diseases: $147,758.00
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