Class IA molecules play a major role in the presentation of peptide epitopes from intracellular parasites to CD8 T cells. Class IB molecules are not as polymorphic as class IA and their function is less well understood. We plan to utilize H-2b mice that have their class IA (KbDb) genes deleted. Unlike previously described class I deficient animals (beta-2M-/- and Tap-1-/-) these mice have a complete absence of class IA molecules but retain class IB expression. They will be tested for their ability to respond to 3 intracellular pathogens, Listeria monocytogenes (LM), vaccinia virus, and vesicular stomatitis virus. CD8 cells are known to play a role in resistance to these pathogens and in the case of LM, it is known that CTL can be generated in vitro against this pathogen presented by 2 class IB molecules, M3 and Qa-1b. The role that class IB molecules play in these infections in providing immunity will be analyzed by assessing the role of various T cell subsets as well as NK cells in vivo. We will also analyze these responses in vitro and identify the epitopes presented by class IB molecules to antigen specific CD8 cells. Finally, since Kb-/-Db-/- mice cannot generate their CD8 repertoire on class IA molecules, we will determine whether these animals have a repertoire directed against both self H-2b class IA molecules as well as other class IA alloantigens.
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