ROLE OF CLASS IB ANTIGENS AND OPPORTUNISTIC INFECTIONS

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DESCRIPTION (Adapted from applicant's abstract): The non-classical class Ib molecule, Qa-1, presents a synthetic copolymer to gamma/delta (gamma/delta) T cells. The investigator has now identified an endogenous nonamer peptide (termed Qdm) that Qa-1b presents to peptide-specific alloreactive alpha/beta (alpha/beta) T cells. With this Qdm probe, the investigator is now in a unique position to determine how class I molecules present alpha/beta T cells vs. gamma/delta ligands to their respective T cells. In addition, Dr. Forman will establish what role this molecule plays in presenting epitopes from two pathogenic microorganisms, L. monocytogenes and MHV to CD8+ cells. To dissect Qa-1b presentation of alpha/beta vs. gamma/delta ligands, the investigator will use Qdm as a ligand for alpha/beta T cells, and the copolymer GluTyr (GT) and M. bovis Hsp65 peptides as a ligand for gamma/delta T cells. He will determine whether GT or Hsp65 competes with Qdm-peptide for presentation to Qdm-specific alpha/beta cytotoxic T lymphocytes (CTL). Conversely, the investigator will determine whether the Qdm-peptide competes for the ability of Qa-1b to present GT to antigen specific gamma/delta T cells. These experiments will be extended by antigen binding and competition assays. Qa-1b will also be subjected to mutagenesis of amino acids located within or out of the antigen binding pocket to determine how this affects presentation of alpha/beta vs gamma/delta ligands. 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. The investigator will synthesize peptides with a putative Qa-1b binding motif and/or extract the peptide(s) from infected cells and determine its identity. MHV is a commonly studied coronavirus and is a frequent cause of common colds in man. This virus contains the Qdm-peptide sequence and thus Qa-1b should be able to present this epitope to CD8+ T cells. The investigator will determine the immune response to this virus in mice that either naturally contain or lack the Qdm-peptide.