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Do class Ib MHC-restricted T cells protect
against Listeria monocytogenes and Shigella flexneri infection?
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Kara Giddings |
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Class I MHC molecules, which present antigenic
peptides to CD8+ cytotoxic T lymphocytes (CTL), can be broadly
classified into two groups: class Ia MHC and class Ib MHC.
In the mouse there are three class Ia MHC molecules (K, D,
and L) each of which shows a high degree of polymorphism and
is found at relatively high concentration on the surface of
all nucleated cells. Class Ib MHC display a more limited polymorphism
and are found at much lower levels on the cell surface. At
least thirty class Ib genes have been identified in the mouse,
but only a handful have been well-characterized to date. Very
little is known about the antigens recognized by class Ib-restricted
CTL, and the ability of these cells participate in a protective
immune response. We are using class Ia MHC-deficient mice
(K-/- D-/- L-/-) and a systemic model of Listeria monocytogenes
infection to determine what role class Ib MHC-restricted CTL
play in generating protective immunity against intracellular
pathogens.
Like L. monocytogenes, Shigella
flexneri also escapes into the cytoplasm of host cells.
Therefore it would be expected that CD8+ T-cells might respond
to proteins secreted by Shigella, and that they might
play a role in limiting bacterial spread. We are employing
a variety of in vivo and in vitro experimental
approaches to define what role, if any, CD8+ T-cells play
in protective immunity to this pathogen which is responsible
for bacillary dysentery.
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