Translation in Immunity

National Institute Of Allergy And Infectious Diseases

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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, the site of class I biogenesis. Following activation, lymphocytes can divide at dizzying rates (with cell cycles as rapid as 2 hr). We are studying the adaptions in translation that make this possible. Our findings suggest that the assumption that lymphocytes must synthesize all of the proteins required for division may not be true. Many other immune cells also demonstrate greatly increased translation following activation by viral infections or other insults. We are using a newly developed technique to study immune cell activation in tissue sections and also via flow cytometry, which has led to novel insights into immune cell function.