Exact prediction of a natural T cell epitope

Rötzschke, Olaf; Falk, Kirsten; Stevanović, Stefan; Jung, Günther; Walden, Peter; Rammensee, Hans‐Georg

doi:10.1002/eji.1830211136

Cited by 410 publications

(243 citation statements)

References 12 publications

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“…Assuming that bona fide MHC-dependent peptides were present at very low concentrations, we reasoned that they would be missed in MS analyses due to the presence of a multitude of other, more abundant peptides. In fact, control experiments showed that a synthetic MHC peptide spiked into urine is not reproducibly detected at concentrations below 10 À 11 M. Therefore, we developed a highly specific model system based on the well-studied H2-K b -presented peptide SIINFEKL corresponding to amino-acid residues 257-264 of chicken ovalbumin (OVA) 40,41 . The transgenic mouse line B6/OVA þ expresses a cell surface protein composed of the entire chicken ovalbumin sequence and a transmembrane sequence under the control of the chicken b-actin promoter in all organs.…”

Section: Isolation and Analysis Of Urinary Peptides By Mass Spectromementioning

confidence: 99%

Mouse urinary peptides provide a molecular basis for genotype discrimination by nasal sensory neurons

et al. 2013

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Selected groups of peptides, including those that are presented by major histocompatibility complex (MHC) proteins, have been proposed to transmit information to the olfactory system of vertebrates via their ability to stimulate chemosensory neurons. However, the lack of knowledge about such peptides in natural sources accessible for nasal recognition has been a major barrier for this hypothesis. Here we analyse urinary peptides from selected mouse strains with respect to genotype-related individual differences. We discover many abundant peptides with single amino-acid variations corresponding to genomic differences. The polymorphism of major urinary proteins is reflected by variations in prominent urinary peptides. We also demonstrate an MHC-dependent peptide (SIINFEKL) occurring at very low concentrations in mouse urine. Chemoreceptive neurons in the vomeronasal organ detect and discriminate single amino-acid variation peptides as well as SIINFEKL. Hence, urinary peptides represent a real-time sampling of the expressed genome available for chemosensory assessment by other individuals.

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Section: Isolation and Analysis Of Urinary Peptides By Mass Spectromementioning

confidence: 99%

Mouse urinary peptides provide a molecular basis for genotype discrimination by nasal sensory neurons

et al. 2013

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“…The 0h-, 8 h-and 48h-DC were loaded with the peptide SIINFEKL [34] at a concentration (100 nM) that in preliminary experiments (peptide range 1-1000 nM) favored the induction of the highest percentage of Tc2 cells, and cultured together with naive OT-1 cells, a homogeneous population of TCR-transgenic CD8 + cells [35], in the presence or absence of optimal amounts of IL-12 or IL-4. Seven days later, cells were collected and assessed for cytokine production by flow cytometry.…”

Section: Resultsmentioning

confidence: 99%

“…Hence, we assessed the capacity of DC at various activation stages to induce polarization of a transgenic T cell population with a different specificity, i.e. cells from TCR7 mice expressing a TCR specific for the epitope 33-41 of lymphocytic choriomeningitis virus (LCMV) glycoprotein 1 (gp [33][34][35][36][37][38][39][40][41] ) [37,38]. In this set of experiments we also tested CpG as pro-maturation stimulus (see Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

“…DO11.10 mice express a Tg ab TCR specific for OVA 323-339 presented in the context of I-A d molecules. LCMV gp33 mice, which express a TCR specific for gp [33][34][35][36][37][38][39][40][41] in association with H-2D b [37], were backcrossed onto C57BL/6 background over six generations to obtain TCR7 mice [38]. All mice were housed in a specific pathogen-free animal facility, and treated in accordance with the European Union Guidelines together with the approval of the Institutional Ethics Committee.…”

Section: Discussionmentioning

confidence: 99%

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Prolonged exposure of dendritic cells to maturation stimuli favors the induction of type‐2 cytotoxic T lymphocytes

Boni¹,

Iezzi

Degl’Innocenti³

et al. 2006

Eur J Immunol

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Dendritic cell (DC) maturation influences the priming and polarization of T lymphocytes. We recently found that early activated DC (i.e. DC exposed to promaturation stimuli for 8 h) were more prone to prime in vivo a type-1 cytotoxic T cell (Tc1) response than DC exposed to pro-maturation stimuli for 48 h (48h-DC). We investigated whether 48h-DC, conversely, allowed the induction of Tc2 cells. Antigenpulsed mouse bone-marrow-derived DC at any maturation stage, in the presence of exogenous IL-12, skewed in vitro naive CD8 + T cells towards Tc1 cells, but 48h-DC most potently, in the presence of exogenous IL-4, favored the induction of Tc2 cells. In vivo, full maturation of DC promoted expansion of Tc2 and fall of Tc1 cells. Tc2 cells maintained a high cytolytic activity and produced significant amounts of IL-4, IL-5, IL-10 and TGF-b. Our results indicate that polarization of naive CD8 + T cells to Tc2 cells is dependent on the amount of time DC have been exposed to maturation stimuli, and might be favored in late and/or chronic phases of an immune response.Supporting information for this article is available at http://www.wiley-vch.de/contents/jc_2040/2006/35597_s.pdf IntroductionUpon antigenic stimulation, T lymphocytes proliferate and acquire a variety of effector functions. Indeed, activation of naive CD4 + T cells in the presence of IL-12 results in the development of Th1 cells, which mainly secrete interferon (IFN)-c, interleukin (IL)-2, tumor necrosis factor (TNF)-a and lymphotoxin, and are commonly associated with a cell-mediated immune response. Conversely, the presence of IL-4 skews the Th response towards Th2 cells producing IL-4, IL-10 and IL-13, relevant cytokines against helminthiasis and allergic diseases [1]. More recently, a third subset of CD4 + T cells has been identified, which express CD25, produce IL-10 and TGF-b, and display regulatory functions [2].The polarization of CD8 + CTL has been less characterized [3]. IL-12 also appears to be critical for the generation of Tc1 cells, characterized by a high production level of IFN-c and cytolytic activity, CC chemokine receptor (CCR)5 expression and the ability to migrate to the inflamed tissues where they are [16], and in many cases their presence was associated with disease severity and progression [13][14][15][16]. In mouse tumor models, IL-4-transduced tumor cells elicited potent antitumor activities [17] and induced Tc2 cells able to cure lung metastases [5,17]. IL-4 produced by CTL was required for the generation of protective tumor-associated CD8 + T cells [5,18]. In other models, Tc2 cells were far less effective in curing subcutaneous tumors [19,20] and lung metastases [21]. Finally, CD8 + T cell subpopulations exhibiting regulatory function have also been described [14,22].Dendritic cells (DC), professional antigen presenting cells (APC) with a unique ability in priming T cell responses [23], play a key role in T cell polarization. In particular, it has been reported that subsets of DC, derived from distinct precursors, induce differenti...

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“…It is a well established phenomenon in the T-cell antigen complex, MHC ''peptide receptor'' system that encodes the intracellular presence of a specific protein via a short peptide on its surface. [127][128][129] In addition, the sequence of ''hydrophobic fingers,'' suggested as a physical expression of the condensed protein code in MHC peptides 128 may be related to the ligand-protein interactions pre- dicated on similarities in their hydrophobic autocorrelation eigenvectors. 1,4,7,16 A similar manifestation of short peptide signaling of a large protein in immunological systems is evidenced by the successful use of protein analogue peptides as ''protein mimetic'' short peptide antigens.…”

Section: Discussionmentioning

confidence: 99%

Designing allosteric peptide ligands targeting a globular protein

et al. 2006

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Patented signal analytic algorithms applied to hydrophobically transformed, numerical amino acid sequences have previously been used to design short, protein‐targeted, L or D retro‐inverso peptides. These peptides have demonstrated allosteric and/or indirect agonist effects on a variety of G‐protein and tyrosine kinase coupled membrane receptors with 30% to over 80% hit rates. Here we extend these approaches to a globular protein target. We designed eight peptide ligands targeting an ELISA antibody responsive protein, β‐galactosidase, βGAL. Three of the eight 14mer peptides allosterically activated βGAL with ELISA methodology. Using Bayesian statistics, this 38% hit rate would have occurred 2 × 10−9 by chance. These peptides demonstrated binding site competitive or noncompetitive interactions, suggesting allosteric site multiplicity with respect to their βGAL binding‐mediated ELISA signal. Kinetic studies demonstrated the temperature dependence of the βGAL peptide binding functions. Using the van't Hoff relation, we found evidence for enthalpy–entropy compensation. This relation is often found for hydrophobic interactions in aqueous media, and is consistent with the postulated hydrophobic series encoding underlying our protein‐targeted, peptide design methods. It appears that our algorithmic, hydrophobic autocovariance eigenvector template approach to the design of allosteric peptides targeting membrane receptors may also be applicable to the design of peptide ligands targeting nonmembrane involved globular proteins. © 2006 Wiley Periodicals, Inc. Biopolymers 85: 38–59, 2007.This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com

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Exact prediction of a natural T cell epitope

Cited by 410 publications

References 12 publications

Mouse urinary peptides provide a molecular basis for genotype discrimination by nasal sensory neurons

Mouse urinary peptides provide a molecular basis for genotype discrimination by nasal sensory neurons

Prolonged exposure of dendritic cells to maturation stimuli favors the induction of type‐2 cytotoxic T lymphocytes

Designing allosteric peptide ligands targeting a globular protein

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