title: Lipopeptides: a novel antigen repertoire presented by major histocompatibility complex class I molecules.
abstract: Post-translationally modified peptides, such as those containing either phosphorylated or O-glycosylated serine/threonine residues, may be presented to cytotoxic T lymphocytes (CTLs) by MHC class I molecules. Most of these modified peptides are captured in the MHC class I groove in a similar manner to that for unmodified peptides. N-Myristoylated 5-mer lipopeptides have recently been identified as a novel chemical class of MHC class I-presented antigens. The rhesus classical MHC class I allele, Mamu-B*098, was found to be capable of binding N-myristoylated lipopeptides and presenting them to CTLs. A high-resolution X-ray crystallographic analysis of the Mamu-B*098:lipopeptide complex revealed that the myristic group as well as conserved C-terminal serine residue of the lipopeptide ligand functioned as anchors, whereas the short stretch of three amino acid residues located in the middle of the lipopeptides was only exposed externally with the potential to interact directly with specific T-cell receptors. Therefore, the modes of lipopeptide-ligand interactions with MHC class I and with T-cell receptors are novel and fundamentally distinct from that for MHC class I-presented peptides. Another lipopeptide-presenting MHC class I allele has now been identified, leading us to the prediction that MHC class I molecules may be separated on a functional basis into two groups: one presenting long peptides and the other presenting short lipopeptides. Since the N-myristoylation of viral proteins is often linked to pathogenesis, CTLs capable of sensing N-myristoylation may serve to control pathogenic viruses, raising the possibility for the development of a new type of lipopeptide vaccine.
authors.affiliation: Laboratory of Cell Regulation, Institute for Virus Research, Kyoto University, Kyoto, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Morita
authors.affiliation: Laboratory of Cell Regulation, Institute for Virus Research, Kyoto University, Kyoto, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Sugita
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000956:Antigens, Viral / Q000276:immunology / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D055666:Lipopeptides / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014765:Viral Vaccines; D014777:Virus Diseases / Q000276:immunology*
chemical_list: D000956:Antigens, Viral; D015395:Histocompatibility Antigens Class I; D055666:Lipopeptides; D014765:Viral Vaccines
keywords: antigen presentation/processing; major histocompatibility complex; structural biology/crystallography