The Immune Epitope Database and Analysis Resource: From Vision to Blueprint

Peters, Bjoern; Sidney, John; Bourne, Phil; Bui, Huynh-Hoa; Buus, Søren; Doh, Grace; Fleri, Ward; Kronenberg, M.; Kubo, Ralph T.; Lund, Ole; Nemazee, David; Ponomarenko, Julia; Sathiamurthy, Muthu; Schoenberger, Stephen P.; Stewart, Scott J.; Surko, Pamela; Way, Scott; Wilson, Steve; Sette, Alessandro

doi:10.1371/journal.pbio.0030091

Cited by 351 publications

(333 citation statements)

References 3 publications

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“…This allowed verifying the peptide sequences and provided a list of positively validated peptides. These peptides were searched against the two databases: SYFPEI-THI (www.syfpeithi.de) and the Immune Epitope Database and Analysis Resource (IEDB; www.immuneepitope.org; Peters et al 2005), which contain reported HLA class I and class II epitopes. The sequences of potential HLA class I epitopes were assessed using the binding motifs shown in SYFPEITHI.…”

Section: Methodsmentioning

confidence: 99%

Identification of potential HLA class I and class II epitope precursors associated with heat shock protein 70 (HSPA)

Stocki

Morris

Preisinger

et al. 2010

Cell Stress and Chaperones

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Heat shock protein 70 (HSPA) is a molecular chaperone which has been suggested to shuttle human leukocyte antigen (HLA) epitope precursors from the proteasome to the transporter associated with antigen processing. Despite the reported observations that peptides chaperoned by HSPA are an effective source of antigens for cross-priming, little is known about the peptides involved in the process. In this study, we investigated the possible involvement of HSPA in HLA class I or class II antigen presentation and analysed the antigenic potential of the associated peptides. HSPA was purified from CCRF-CEM and K562 cell lines, and using mass spectrometry techniques, we identified 44 different peptides which were copurified with HSPA. The affinity of the identified peptides to two HSPA isoforms, HSPA1A and HSPA8, was confirmed using a peptide array. Four of the HSPAassociated peptides were matched with 13 previously reported HLA epitopes. Of these 13 peptides, nine were HLA class I and four were HLA class II epitopes. These results demonstrate the association of HSPA with HLA class I and class II epitopes, therefore providing further evidence for the involvement of HSPA in the antigen presentation process.

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Section: Methodsmentioning

confidence: 99%

Identification of potential HLA class I and class II epitope precursors associated with heat shock protein 70 (HSPA)

Stocki

Morris

Preisinger

et al. 2010

Cell Stress and Chaperones

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“…To date, only four HLA-A3-restricted T cell epitopes have been identified in melanoma-associated proteins, all of them derived from the gp100 antigen (16)(17)(18). We designed a library of peptides derived from the melanocyte differentiation antigens (gp100, mart-1, tyrosinase, and tyrosine-related-protein-1 and -2), plus the melanoma-associated protein Nodal (19) by using three binding prediction algorithms for HLA-A3 (9,20). The resulting 203 peptides (SI Table 3) were then analyzed for HLA-A3 binding in a fluorescence polarization assay.…”

Section: Identification Of Melanoma-associated Hla-a3 Ligandsmentioning

confidence: 99%

Conditional MHC class I ligands and peptide exchange technology for the human MHC gene products HLA-A1, -A3, -A11, and -B7

Bakker¹,

Hoppes

Linnemann³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

135

167

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Major histocompatibility complex (MHC) class I multimer technology has become an indispensable immunological assay system to dissect antigen-specific cytotoxic CD8 ؉ T cell responses by flow cytometry. However, the development of high-throughput assay systems, in which T cell responses against a multitude of epitopes are analyzed, has been precluded by the fact that for each T cell epitope, a separate in vitro MHC refolding reaction is required. We have recently demonstrated that conditional ligands that disintegrate upon exposure to long-wavelength UV light can be designed for the human MHC molecule HLA-A2. To determine whether this peptide-exchange technology can be developed into a generally applicable approach for high throughput MHC based applications we set out to design conditional ligands for the human MHC gene products HLA-A1, -A3, -A11, and -B7. Here, we describe the development and characterization of conditional ligands for this set of human MHC molecules and apply the peptide-exchange technology to identify melanoma-associated peptides that bind to HLA-A3 with high affinity. The conditional ligand technology developed here will allow high-throughput MHC-based analysis of cytotoxic T cell immunity in the vast majority of Western European individuals.M HC Class I molecules are heterotrimeric complexes consisting of an invariant light chain called ␤2-microglobulin (␤2m), a polymorphic heavy chain (HC) and an Ϸ8-to 11-aa peptide ligand. These peptide-MHC (pMHC) complexes are recognized by the T cell receptor (TCR) of CD8 ϩ T cells in a peptide-specific fashion, and this interaction forms the molecular basis of antigen recognition by CD8 ϩ T cells. In the past decade, the mapping of pathogen-specific and autoimmune-or cancer-associated T cell epitopes has been a major driving force in the development of assay systems for immunomonitoring. In addition, knowledge of such T cell epitopes forms a cornerstone in the development of vaccine-based or adoptive T cell therapies. As a first step in the mapping of disease-associated T cell epitopes, peptide fragments of disease-associated proteomes may be analyzed for binding to MHC molecules of interest, and subsequent assays can then be used to determine whether T cell reactivity against such pMHC complexes does occur. As demonstrated in a landmark study by Altman and colleagues (1), such antigen-specific T cell reactivity can efficiently be detected by the staining of T cell populations with recombinant fluorescent multimeric MHC molecules.There is an increasing interest in the development of assay systems, such as MHC-based microarrays, that can monitor a multitude of T cell responses in parallel (2-4). Unfortunately, current technology does not allow for the high-throughput generation of different pMHC complexes, thereby limiting the utility of these techniques. Specifically, because MHC class I complexes that are devoid of peptide are markedly unstable (5, 6), current production processes for recombinant MHC complexes require inclusion of a specific T cell epi...

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“…To discriminate infected or malignant cells from normal cells, the CD8 T cell must detect disease-associated, processed peptide epitopes bound to self major histocompatibility complex class I (MHC-I) 2 molecules. The feasibility of identifying disease-associated epitopes was first demonstrated by Thierry Boon and co-workers (1) using a mouse model of tumor rejection.…”

mentioning

confidence: 99%

“…The feasibility of identifying disease-associated epitopes was first demonstrated by Thierry Boon and co-workers (1) using a mouse model of tumor rejection. Since then, many clinically relevant peptide epitopes have been identified for class I human leukocyte antigens (HLA-I) (2). A few examples include HLA-A2-restricted epitopes from human T-lymphotropic virus (HTLV) (3), influenza A (4), and melanoma (5).…”

mentioning

confidence: 99%

Human Major Histocompatibility Complex (MHC) Class I Molecules with Disulfide Traps Secure Disease-related Antigenic Peptides and Exclude Competitor Peptides

Truscott

Wang

Lybarger

et al. 2008

Journal of Biological Chemistry

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The ongoing discovery of disease-associated epitopes detected by CD8 T cells greatly facilitates peptide-based vaccine approaches and the construction of multimeric soluble recombinant proteins (e.g. tetramers) for isolation and enumeration of antigen-specific CD8 T cells. Related to these outcomes of epitope discovery is the recent demonstration that MHC class I/peptide complexes can be expressed as single chain trimers (SCTs) with peptide, ␤ 2 m and heavy chain connected by linkers to form a single polypeptide chain. Studies using clinically relevant mouse models of human disease have shown that SCTs expressed by DNA vaccination are potent stimulators of cytotoxic T lymphocytes. Their vaccine efficacy has been attributed to the fact that SCTs contain a preprocessed and preloaded peptide that is stably displayed on the cell surface. Although SCTs of HLA class I/peptide complexes have been previously reported, they have not been characterized for biochemical stability or susceptibility to exogenous peptide binding. Here we demonstrate that human SCTs remain almost exclusively intact when expressed in cells and can incorporate a disulfide trap that dramatically excludes the binding of exogenous peptides. The mechanistic and practical applications of these findings for vaccine development and T cell isolation/enumeration are discussed.

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The Immune Epitope Database and Analysis Resource: From Vision to Blueprint

Abstract: A planned repository of immune epitope data with associated analysis tools should be a boon to vaccine development

Cited by 351 publications

References 3 publications

Identification of potential HLA class I and class II epitope precursors associated with heat shock protein 70 (HSPA)

Identification of potential HLA class I and class II epitope precursors associated with heat shock protein 70 (HSPA)

Conditional MHC class I ligands and peptide exchange technology for the human MHC gene products HLA-A1, -A3, -A11, and -B7

Human Major Histocompatibility Complex (MHC) Class I Molecules with Disulfide Traps Secure Disease-related Antigenic Peptides and Exclude Competitor Peptides

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