Translation in Immunity

National Institute Of Allergy And Infectious Diseases

Investigators

Linked publications & trials

Abstract

Class I molecules of the major histocompatibility complex (MHC) bind short peptides and present them to CD8+ T cells. CD8 positive T-cells play a critical role in eradicating intracellular pathogens (particularly viruses) and tumors. Nearly all viral peptides appear to derive from DRiPs (defective ribosomal products); rapidly degraded nascent proteins that fail to achieve a stable native conformation due to mistranslation, misfolding, mistargeting, or stoichiometric excess. We are characterizing all aspects of DRiP synthesis, degradation, and loading of DRiP-derived peptides onto class I molecules in the endoplasmic reticulum (ER), the site of class I biogenesis. We are also studying peptide transport into the ER using a novel assay devised in my laboratory. Using this assay in collaboration with NCATs, we have discovered a cell-permeable small molecule TAP inhibitor.