The C-terminal extension landscape of naturally presented HLA-I ligands.

Abstract:

:HLA-I molecules play a central role in antigen presentation. They typically bind 9- to 12-mer peptides, and their canonical binding mode involves anchor residues at the second and last positions of their ligands. To investigate potential noncanonical binding modes, we collected in-depth and accurate HLA peptidomics datasets covering 54 HLA-I alleles and developed algorithms to analyze these data. Our results reveal frequent (442 unique peptides) and statistically significant C-terminal extensions for at least eight alleles, including the common HLA-A03:01, HLA-A31:01, and HLA-A68:01. High resolution crystal structure of HLA-A68:01 with such a ligand uncovers structural changes taking place to accommodate C-terminal extensions and helps unraveling sequence and structural properties predictive of the presence of these extensions. Scanning viral proteomes with the C-terminal extension motifs identifies many putative epitopes and we demonstrate direct recognition by human CD8+ T cells of a 10-mer epitope from cytomegalovirus predicted to follow the C-terminal extension binding mode.

authors

Guillaume P,Picaud S,Baumgaertner P,Montandon N,Schmidt J,Speiser DE,Coukos G,Bassani-Sternberg M,Filippakopoulos P,Gfeller D

doi

10.1073/pnas.1717277115

subject

Has Abstract

pub_date

2018-05-15 00:00:00

pages

5083-5088

issue

20

eissn

0027-8424

issn

1091-6490

pii

1717277115

journal_volume

115

pub_type

杂志文章
  • The three-dimensional structure of an H-2Ld-peptide complex explains the unique interaction of Ld with beta-2 microglobulin and peptide.

    abstract::Solution at 2.5-A resolution of the three-dimensional structure of H-2Ld with a single nine-residue peptide provides a structural basis for understanding its unique interaction with beta-2 microglobulin (beta2m) and peptide. Consistent with the biological data that show an unusually weak association of Ld with beta2m,...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.94.13.6880

    authors: Balendiran GK,Solheim JC,Young AC,Hansen TH,Nathenson SG,Sacchettini JC

    更新日期:1997-06-24 00:00:00

  • The self-control consequences of political ideology.

    abstract::Evidence from three studies reveals a critical difference in self-control as a function of political ideology. Specifically, greater endorsement of political conservatism (versus liberalism) was associated with greater attention regulation and task persistence. Moreover, this relationship is shown to stem from varying...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1503530112

    authors: Clarkson JJ,Chambers JR,Hirt ER,Otto AS,Kardes FR,Leone C

    更新日期:2015-07-07 00:00:00

  • A helical-dipole model describes the single-channel current rectification of an uncharged peptide ion channel.

    abstract::We are designing simple peptide ion channels as model systems for the study of the physical principles controlling conduction through ion-channel proteins. Here we report on an uncharged peptide, Ac-(Leu-Ser-Ser-Leu-Leu-Ser-Leu)3-CONH2, designed to form an aggregate of parallel, amphiphilic, membrane-spanning alpha-he...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.91.11.4859

    authors: Kienker PK,DeGrado WF,Lear JD

    更新日期:1994-05-24 00:00:00

  • A new ultrafast energy funneling material harvests three times more diffusive solar energy for GaInP photovoltaics.

    abstract::There is no theoretical limit in using molecular networks to harvest diffusive sun photons on large areas and funnel them onto much smaller areas of highly efficient but also precious energy-converting materials. The most effective concept reported so far is based on a pool of randomly oriented, light-harvesting donor...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.2019198117

    authors: Willich MM,Wegener L,Vornweg J,Hohgardt M,Nowak J,Wolter M,Jacob CR,Walla PJ

    更新日期:2020-12-29 00:00:00

  • Acquisition of a determinant for chloramphenicol resistance by coliphage lambda.

    abstract::A determinanat for chloramphenicol resistance, cam, initially detected on a resistance transfer factor (RTF) and since transferred to phage P1, may be acquired from P1 by coliphage lambda. Lambdapcam are obtained when a lambda prophage is induced in bacteria which also harbor P1 cam prophage. Lambdacam formation is no...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.72.12.5041

    authors: Gottesman MM,Rosner JL

    更新日期:1975-12-01 00:00:00

  • Defective N-acetylaspartate catabolism reduces brain acetate levels and myelin lipid synthesis in Canavan's disease.

    abstract::Canavan's disease (CD) is a fatal, hereditary disorder of CNS development that has been linked to mutations in the gene for the enzyme aspartoacylase (ASPA) (EC 3.5.1.15). ASPA acts to hydrolyze N-acetylaspartate (NAA) into l-aspartate and acetate, but the connection between ASPA deficiency and the failure of proper C...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0409184102

    authors: Madhavarao CN,Arun P,Moffett JR,Szucs S,Surendran S,Matalon R,Garbern J,Hristova D,Johnson A,Jiang W,Namboodiri MA

    更新日期:2005-04-05 00:00:00

  • Human cytomegalovirus latent infection of granulocyte-macrophage progenitors.

    abstract::We have investigated the interaction of human cytomegalovirus (CMV) with cultured primary granulocyte-macrophage progenitors, a suspected natural site of viral latency, and have established conditions for latent infection and reactivation in this cell population. Progenitor cells from human fetal liver or bone marrow ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.91.25.11879

    authors: Kondo K,Kaneshima H,Mocarski ES

    更新日期:1994-12-06 00:00:00

  • Central role for hydrogen peroxide in P2Y1 ADP receptor-mediated cellular responses in vascular endothelium.

    abstract::ADP activates a family of cell surface receptors that modulate signaling pathways in a broad range of cells. ADP receptor antagonists are widely used to treat cardiovascular disease states. These studies identify a critical role for the stable reactive oxygen species hydrogen peroxide (H2O2) in mediating cellular resp...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1320854111

    authors: Kalwa H,Sartoretto JL,Martinelli R,Romero N,Steinhorn BS,Tao M,Ozaki CK,Carman CV,Michel T

    更新日期:2014-03-04 00:00:00

  • Early stages in DNA binding and uptake during genetic transformation of pneumococci.

    abstract::Ethylenediaminetetraacetate and other divalent-cation-complexing agents greatly stimulate the cellular binding of DNA molecules to competent pneumococci, while the appearance of genetic transformants and nuclease-resistant DNA binding are completely inhibited. Based on this finding, we developed an experimental system...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.71.4.1493

    authors: Seto H,Tomasz A

    更新日期:1974-04-01 00:00:00

  • Deactivation of phosphatidylinositol 3,4,5-trisphosphate/Akt signaling mediates neutrophil spontaneous death.

    abstract::Neutrophil spontaneous death plays essential roles in neutrophil homeostasis and resolution of inflammation, whereas the underlying molecular mechanisms are still ill-defined. Neutrophils die because of programmed cell death or apoptosis. However, treatment with inhibitor of caspases, which are responsible for the maj...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0605722103

    authors: Zhu D,Hattori H,Jo H,Jia Y,Subramanian KK,Loison F,You J,Le Y,Honczarenko M,Silberstein L,Luo HR

    更新日期:2006-10-03 00:00:00

  • Acrosin is essential for sperm penetration through the zona pellucida in hamsters.

    abstract::During natural fertilization, mammalian spermatozoa must pass through the zona pellucida before reaching the plasma membrane of the oocyte. It is assumed that this step involves partial lysis of the zona by sperm acrosomal enzymes, but there has been no unequivocal evidence to support this view. Here we present eviden...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1917595117

    authors: Hirose M,Honda A,Fulka H,Tamura-Nakano M,Matoba S,Tomishima T,Mochida K,Hasegawa A,Nagashima K,Inoue K,Ohtsuka M,Baba T,Yanagimachi R,Ogura A

    更新日期:2020-02-04 00:00:00

  • Appearance of acetylcholine receptors during differentiation of a myogenic cell line.

    abstract::Acquisition of acetylcholine receptors during differentiation of a clonal myoblast cell line was monitored with a neurotoxin isolated from venom of the Indian Cobra Naja naja. Toxin bound specifically and reversibly to acetylcholine receptors of the differentiated cells. Specificity of the binding reaction was assayed...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.69.10.2762

    authors: Patrick J,Heinemann SF,Lindstrom J,Schubert D,Steinbach JH

    更新日期:1972-10-01 00:00:00

  • Overexpressed Ly-6A.2 mediates cell-cell adhesion by binding a ligand expressed on lymphoid cells.

    abstract::The Ly-6 locus encodes several cell surface proteins whose functions are unknown. Although it is hypothesized that these proteins may be receptors, there is no direct evidence that they bind a ligand. Herein we present evidence that Ly-6A.2, a Ly-6 protein expressed on T lymphocytes, binds a ligand expressed on normal...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.92.10.4294

    authors: Bamezai A,Rock KL

    更新日期:1995-05-09 00:00:00

  • A position 12-activated H-ras oncogene in all HS578T mammary carcinosarcoma cells but not normal mammary cells of the same patient.

    abstract::Among 21 human mammary tumors analyzed for transforming genes by transfection of NIH/3T3 cells, only DNA of a carcinosarcoma cell line, HS578T, registered as positive. A Harvey (H)-ras oncogene identified in this line was cloned in biologically active form and the activating lesion was identified as a single nucleotid...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.81.17.5384

    authors: Kraus MH,Yuasa Y,Aaronson SA

    更新日期:1984-09-01 00:00:00

  • Anti-SIRPα antibody immunotherapy enhances neutrophil and macrophage antitumor activity.

    abstract::Cancer immunotherapy has emerged as a promising therapeutic intervention. However, complete and durable responses are only seen in a fraction of patients who have cancer. A key factor that limits therapeutic success is the infiltration of tumors by cells of the myeloid lineage. The inhibitory receptor signal regulator...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1710877114

    authors: Ring NG,Herndler-Brandstetter D,Weiskopf K,Shan L,Volkmer JP,George BM,Lietzenmayer M,McKenna KM,Naik TJ,McCarty A,Zheng Y,Ring AM,Flavell RA,Weissman IL

    更新日期:2017-12-05 00:00:00

  • Rotavirus mRNAS are released by transcript-specific channels in the double-layered viral capsid.

    abstract::Rotaviruses are the single most common cause of fatal and severe childhood diarrheal illness worldwide (>125 million cases annually). Rotavirus shares structural and functional features with many viruses, such as the presence of segmented double-stranded RNA genomes selectively and tightly packed with a conserved numb...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1220345110

    authors: Periz J,Celma C,Jing B,Pinkney JN,Roy P,Kapanidis AN

    更新日期:2013-07-16 00:00:00

  • Human eIF4E promotes mRNA restructuring by stimulating eIF4A helicase activity.

    abstract::Elevated eukaryotic initiation factor 4E (eIF4E) levels frequently occur in a variety of human cancers. Overexpression of eIF4E promotes cellular transformation by selectively increasing the translation of proliferative and prosurvival mRNAs. These mRNAs possess highly structured 5'-UTRs that impede ribosome recruitme...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1303781110

    authors: Feoktistova K,Tuvshintogs E,Do A,Fraser CS

    更新日期:2013-08-13 00:00:00

  • Glucocorticoid receptor-dependent disruption of a specific nucleosome on the mouse mammary tumor virus promoter is prevented by sodium butyrate.

    abstract::Our laboratory has previously developed cell lines derived from mouse NIH 3T3 fibroblasts and C127 mammary tumor cells that stably express mouse mammary tumor virus (MMTV) long terminal repeat fusion genes in bovine papillomavirus-based episomes. Glucocorticoid hormone strongly activates transcription from episomes an...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.87.10.3977

    authors: Bresnick EH,John S,Berard DS,LeFebvre P,Hager GL

    更新日期:1990-05-01 00:00:00

  • A virion-specific inhibitory molecule with therapeutic potential for human immunodeficiency virus type 1.

    abstract::A potential new approach for gene therapy against human immunodeficiency virus type 1 (HIV-1) infection is the design of a nonstructural gene-based virion-specific inhibitory molecule that is packaged with virus to destroy its infectivity. We tested this approach for HIV-1 by using Vpx, a virion-associated protein of ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.90.8.3544

    authors: Matsuda Z,Yu X,Yu QC,Lee TH,Essex M

    更新日期:1993-04-15 00:00:00

  • Association of cytosol hemoglobin with the membrane in intact erythrocytes.

    abstract::The problem of demonstrating hemoglobin binding to the erythrocyte membrane in intact cells was approached by observing the quenching of fluorescent membrane probes by hemoglobin as a function of pH. This quenching was studied by measuring fluorescence intensities and decay rates of membrane-bound donors by both right...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.79.2.408

    authors: Eisinger J,Flores J,Salhany JM

    更新日期:1982-01-01 00:00:00

  • Thermus thermophilus: a link in evolution of the tRNA-dependent amino acid amidation pathways.

    abstract::Thermus thermophilus possesses an aspartyl-tRNA synthetase (AspRS2) able to aspartylate efficiently tRNAAsp and tRNAAsn. Aspartate mischarged on tRNAAsn then is converted into asparagine by an omega amidase that differs structurally from all known asparagine synthetases. However, aspartate is not misincorporated into ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.95.22.12832

    authors: Becker HD,Kern D

    更新日期:1998-10-27 00:00:00

  • Trigger loop dynamics mediate the balance between the transcriptional fidelity and speed of RNA polymerase II.

    abstract::During transcription, RNA polymerase II (RNAPII) must select the correct nucleotide, catalyze its addition to the growing RNA transcript, and move stepwise along the DNA until a gene is fully transcribed. In all kingdoms of life, transcription must be finely tuned to ensure an appropriate balance between fidelity and ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1200939109

    authors: Larson MH,Zhou J,Kaplan CD,Palangat M,Kornberg RD,Landick R,Block SM

    更新日期:2012-04-24 00:00:00

  • Maladaptive DNA repair is the ultimate contributor to the death of trimethoprim-treated cells under aerobic and anaerobic conditions.

    abstract::The bactericidal effects of antibiotics are undoubtedly triggered by target-specific interactions, but there is growing evidence that an important aspect of cytotoxicity results from treatment-induced metabolic perturbations. In this study, we characterized molecular mechanisms whereby trimethoprim treatment results i...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1706236114

    authors: Giroux X,Su WL,Bredeche MF,Matic I

    更新日期:2017-10-24 00:00:00

  • Inherited genetic variant predisposes to aggressive but not indolent prostate cancer.

    abstract::Autopsy studies suggest that most aging men will develop lesions that, if detected clinically, would be diagnosed as prostate cancer (PCa). Most of these cancers are indolent and remain localized; however, a subset of PCa is aggressive and accounts for more than 27,000 deaths in the United States annually. Identificat...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0914061107

    authors: Xu J,Zheng SL,Isaacs SD,Wiley KE,Wiklund F,Sun J,Kader AK,Li G,Purcell LD,Kim ST,Hsu FC,Stattin P,Hugosson J,Adolfsson J,Walsh PC,Trent JM,Duggan D,Carpten J,Grönberg H,Isaacs WB

    更新日期:2010-02-02 00:00:00

  • Contraction of detergent-treated smooth muscle.

    abstract::After exposure of segments of rabbit taenia coli to the nonionic detergent Triton X-100, tension could be induced by increasing the [Ca2+] in the micromolar range. In the presence of a saturating [Ca2+], this preparation developed nearly 100% of the control tetanus tension recorded from the intact muscle prior to the ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.75.7.3527

    authors: Gordon AR

    更新日期:1978-07-01 00:00:00

  • Regulation of meiotic chromatin loop size by chromosomal position.

    abstract::At meiotic prophase, chromatin loops around a proteinaceous core, with the sizes of these loops varying between species. Comparison of the morphology of sequence-related inserts at different sites in transgenic mice demonstrates that loop size also varies with chromosomal geography. Similarly, chromatin loop lengths d...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.93.7.2795

    authors: Heng HH,Chamberlain JW,Shi XM,Spyropoulos B,Tsui LC,Moens PB

    更新日期:1996-04-02 00:00:00

  • Acetylcholine receptors at neuromuscular synapses: phylogenetic differences detected by snake alpha-neurotoxins.

    abstract::Phylogenetic differences in acetylcholine receptors from skeletal neuromuscular synapses of various species of snakes and lizards have been investigated, using the snake venom alpha-neurotoxins alpha-atratoxin (cobrotoxin) and alpha-bungarotoxin. The acetylcholine receptors of the phylogenetically primitive lizards, l...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.72.8.3245

    authors: Burden SJ,Hartzell HC,Yoshikami D

    更新日期:1975-08-01 00:00:00

  • Strategy for reversing resistance to a single anticancer agent in human prostate and pancreatic carcinomas.

    abstract::Effective therapies for most solid cancers, especially those that have progressed to metastasis, remain elusive because of inherent and acquired resistance of tumor cells to conventional treatments. Additionally, the effective therapeutic window for many protocols can be very narrow, frequently resulting in toxicity. ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0700042104

    authors: Lebedeva IV,Washington I,Sarkar D,Clark JA,Fine RL,Dent P,Curiel DT,Turro NJ,Fisher PB

    更新日期:2007-02-27 00:00:00

  • Defective CD95/APO-1/Fas signal complex formation in the human autoimmune lymphoproliferative syndrome, type Ia.

    abstract::Heterozygous mutations in the CD95 (APO-1/Fas) receptor occur in most individuals with autoimmune lymphoproliferative syndrome (ALPS) and dominantly interfere with apoptosis by an unknown mechanism. We show that local or global alterations in the structure of the cytoplasmic death domain from nine independent ALPS CD9...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.96.8.4552

    authors: Martin DA,Zheng L,Siegel RM,Huang B,Fisher GH,Wang J,Jackson CE,Puck JM,Dale J,Straus SE,Peter ME,Krammer PH,Fesik S,Lenardo MJ

    更新日期:1999-04-13 00:00:00

  • Anti-viral protection conferred by recombinant adenylate cyclase toxins from Bordetella pertussis carrying a CD8+ T cell epitope from lymphocytic choriomeningitis virus.

    abstract::The elucidation of the mechanisms of antigen presentation by major histocompatibility complex class I molecules has stimulated the search for nonreplicative vectors that could deliver CD8+ T cell epitopes to the cytosol of antigen-presenting cells to trigger the activation of specific cytotoxic T lymphocytes (CTLs) in...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.94.7.3314

    authors: Saron MF,Fayolle C,Sebo P,Ladant D,Ullmann A,Leclerc C

    更新日期:1997-04-01 00:00:00