Epitopes described in "Structural basis for the presentation of tumor-associated MHC class II-restricted phosphopeptides to CD4+ T cells."

Reference
Article Authors:Yili Li; Florence R Depontieu; John Sidney; Theresa M Salay; Victor H Engelhard; Donald F Hunt; Alessandro Sette; Suzanne L Topalian; Roy A Mariuzza
Article Title:Structural basis for the presentation of tumor-associated MHC class II-restricted phosphopeptides to CD4+ T cells.
Reference Detail
Reference ID:1019663
Abstract:Dysregulated protein phosphorylation is a hallmark of malignant transformation. Transformation can generate major histocompatibility complex (MHC)-bound phosphopeptides that are differentially displayed on tumor cells for specific recognition by T cells. To understand how phosphorylation alters the antigenic identity of self-peptides and how MHC class II molecules present phosphopeptides for CD4(+) T-cell recognition, we determined the crystal structure of a phosphopeptide derived from melanoma antigen recognized by T cells-1 (pMART-1), selectively expressed by human melanomas, in complex with HLA-DR1. The structure revealed that the phosphate moiety attached to the serine residue at position P5 of pMART-1 is available for direct interactions with T-cell receptor (TCR) and that the peptide N-terminus adopts an unusual conformation orienting it toward TCR. This structure, combined with measurements of peptide affinity for HLA-DR1 and of peptide-MHC recognition by pMART-1-specific T cells, suggests that TCR recognition is focused on the N-terminal portion of pMART-1. This recognition mode appears to be distinct from that of foreign antigen complexes but is remarkably reminiscent of the way autoreactive TCRs engage self- or altered self-peptides, consistent with the tolerogenic nature of tumor-host immune interactions.
Date:2010
Reference Type:Literature
PubMed ID:20417641
Journal:J Mol Biol
Journal Volume:399
Article Pages:596-603
Journal ISSN:1089-8638
Article Chemical List:Antigens, Neoplasm;HLA-DR1 Antigen;MART-1 Antigen;MLANA protein, human;Multiprotein Complexes;Neoplasm Proteins;Peptide Fragments;Phosphopeptides;Receptors, Antigen, T-Cell;Serine
Article MeSH List:Amino Acid Sequence; Antigen Presentation; Antigens, Neoplasm(chemistry; genetics; metabolism); Binding Sites; CD4-Positive T-Lymphocytes(immunology); Crystallography, X-Ray; HLA-DR1 Antigen(chemistry; metabolism); Humans; MART-1 Antigen; Melanoma(immunology); Models, Molecular; Molecular Sequence Data; Multiprotein Complexes; Neoplasm Proteins(chemistry; genetics; metabolism); Peptide Fragments(chemistry; genetics; immunology; metabolism); Phosphopeptides(chemistry; genetics; immunology; metabolism); Phosphorylation; Protein Conformation; Receptors, Antigen, T-Cell(metabolism); Serine(chemistry)
Curation Last Updated:2014-04-01 20:46:50