The goal of this proposal is to define how tapasin regulates the presentation of viral pathogen epitopes by major histocompatibility complex (MHC) class I molecules. The immune system recognizes infected cells via the presentation of pathogen-specific peptide fragments bound to MHC class I heavy chains. These peptides are detected by cytotoxic T lymphocytes that lyse the infected cells. Assembly of the MHC class I heavy chain with peptide and beta2-microglobulin occurs in the endoplasmic reticulum (ER). Among the ER chaperone proteins that associate with MHC class I, the only one dedicated uniquely to assisting MHC class I assembly is tapasin. However, the mechanisms by which tapasin affects antigen presentation are poorly understood. In this study, we will focus on an epitope derived from an NIAID Category A Priority Pathogen, lymphocytic choriomeningitis virus (LCMV). We propose to test the hypothesis that LCMV peptide presentation is influenced by specific tapasin functions. Information gained in this study will contribute to our understanding of the mechanisms of tapasin activity and the regulation of the cellular immune response to LCMV.
| Morris, Chantey R; Reber, Adrian J; Petersen, Jason L et al. (2004) Association of intracellular proteins with folded major histocompatibility complex class I molecules. Immunol Res 30:171-9 |
| Turnquist, Heth R; Petersen, Jason L; Vargas, Shanna E et al. (2004) The Ig-like domain of tapasin influences intermolecular interactions. J Immunol 172:2976-84 |
