title: Presentation of Cryptic Peptides by MHC Class I Is Enhanced by Inflammatory Stimuli.
abstract: Cytolytic T cells eliminate infected or cancer cells by recognizing peptides presented by MHC class I molecules on the cell surface. The antigenic peptides are derived primarily from newly synthesized proteins including those produced by cryptic translation mechanisms. Previous studies have shown that cryptic translation can be initiated by distinct mechanisms at non-AUG codons in addition to conventional translation initiated at the canonical AUG start codon. In this study, we show that presentation of endogenously translated cryptic peptides is enhanced by TLR signaling pathways involved in pathogen recognition as well as by infection with different viruses. This enhancement of cryptic peptides was caused by proinflammatory cytokines, secreted in response to microbial infection. Furthermore, blocking these cytokines abrogated the enhancement of cryptic peptide presentation in response to infection. Thus, presentation of cryptic peptides is selectively enhanced during inflammation and infection, which could allow the immune system to detect intracellular pathogens that might otherwise escape detection because of inhibition of conventional host translation mechanisms.
authors.affiliation: Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720.
authors.forename: Sharanya
authors.identifier: 0000-0002-7021-3664
authors.initials: S
authors.lastname: Prasad
authors.affiliation: Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720.
authors.forename: Shelley R
authors.identifier: 0000-0001-6231-9082
authors.initials: SR
authors.lastname: Starck
authors.affiliation: Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720 nshastri@berkeley.edu.
authors.forename: Nilabh
authors.initials: N
authors.lastname: Shastri
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000956:Antigens, Viral / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D006566:Herpesviridae Infections / Q000276:immunology*; D000949:Histocompatibility Antigens Class II; D007249:Inflammation / Q000276:immunology*; D018836:Inflammation Mediators / Q000378:metabolism; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018146:Muromegalovirus / Q000276:immunology*; D010455:Peptides / Q000276:immunology; D014176:Protein Biosynthesis / Q000276:immunology; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000378:metabolism
chemical_list: D000956:Antigens, Viral; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D018836:Inflammation Mediators; D010455:Peptides; D051193:Toll-Like Receptors