Do class Ib MHC-restricted T cells protect against Listeria monocytogenes and Shigella flexneri infection?

Kara Giddings

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.