QA-1B IN PRESENTATION OF ALPHA/BETA AND GAMMA/DELTA LIGANDS TO T CELLS

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The class I molecule, Qa-1, presents a synthetic copolymer to gamma-delta T cells. We have now identified an endogenous nonamer peptide (termed Qdm) that Qa-1b presents to peptide-specific alloreactive alpha-beta T cells. With this Qdm probe we are now in a unique position to determine how class I molecules present alpha-beta vs. gamma-delta ligands to their respective T cells. In addition we will establish what role this molecule plays in presenting epitopes from two pathogenic microorganisms, Listeria monocytogenes and murine hepatitis virus, to CD8+ cells. To dissect Qa-1b presentation of alpha-beta vs. gamma-delta ligands, we will use Qdm as a ligand for alpha-beta T cells, and (Glu50Tyr50) (abbreviated GT) and M. bovis Hsp65 peptides as a ligand for gamma-delta T cells. We will determine whether GT or Hsp65 competes with Qdm-peptide for presentation to Qdm-specific alpha-beta cytotoxic T lymphocytes (CTL). Conversely, we will determine whether the Qdm-peptide competes for the ability of Qa-1b to present GT to antigen specific gamma-delta hybridomas. These experiments will be extended by antigen binding and competition assays. L. monocytogenes is an opportunistic agent which preferentially infects immunocompromised individuals. An epitope from the listeriolysin O molecule is presented to CTL by Qa-1b. We will synthesize peptides with a putative Qa-1b binding motif and/or extract the peptide(s) from infected cells and determine its identity. Coronavirus and is a frequent cause of common colds in man. Murine hepatitis virus is a commonly studied mouse coronavirus whose HE protein contains the Qdm-peptide sequence. Qa-1b should be able to present this epitope to CD8+ T cells. We will determine the immune response to this virus in mice that either naturally contain or lack the Qdm-peptide.