Identification of an I‐A<sup>d</sup> restricted peptide on the 65‐kilodalton heat shock protein of <i>Mycobacterium avium</i>

Nagabhushanam, Vijaya; Purcell, Anthony W.; Mannering, Stuart I.; Germano, Susie; Praszkier, Judyta; Cheers, Christina

doi:10.1046/j.1440-1711.2002.01128.x

Cited by 4 publications

(3 citation statements)

References 40 publications

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“…We used an independent test data set to evaluate the predictivity of our mouse class II models. Sixty class II epitopes from 21 protein sequences were used in the test set, see Table . − The full protein sequences were retrieved from SWISS−PROT . Complete protein sequences were used as input in this test, and the ability of the algorithm to identify epitopes correctly was assessed.…”

Section: Systems and Methodsmentioning

confidence: 99%

Toward Prediction of Class II Mouse Major Histocompatibility Complex Peptide Binding Affinity: in Silico Bioinformatic Evaluation Using Partial Least Squares, a Robust Multivariate Statistical Technique

Hattotuwagama

Toseland

Guan

et al. 2005

J. Chem. Inf. Model.

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The accurate identification of T-cell epitopes remains a principal goal of bioinformatics within immunology. As the immunogenicity of peptide epitopes is dependent on their binding to major histocompatibility complex (MHC) molecules, the prediction of binding affinity is a prerequisite to the reliable prediction of epitopes. The iterative self-consistent (ISC) partial-least-squares (PLS)-based additive method is a recently developed bioinformatic approach for predicting class II peptide-MHC binding affinity. The ISC-PLS method overcomes many of the conceptual difficulties inherent in the prediction of class II peptide-MHC affinity, such as the binding of a mixed population of peptide lengths due to the open-ended class II binding site. The method has applications in both the accurate prediction of class II epitopes and the manipulation of affinity for heteroclitic and competitor peptides. The method is applied here to six class II mouse alleles (I-Ab, I-Ad, I-Ak, I-As, I-Ed, and I-Ek) and included peptides up to 25 amino acids in length. A series of regression equations highlighting the quantitative contributions of individual amino acids at each peptide position was established. The initial model for each allele exhibited only moderate predictivity. Once the set of selected peptide subsequences had converged, the final models exhibited a satisfactory predictive power. Convergence was reached between the 4th and 17th iterations, and the leave-one-out cross-validation statistical terms--q2, SEP, and NC--ranged between 0.732 and 0.925, 0.418 and 0.816, and 1 and 6, respectively. The non-cross-validated statistical terms r2 and SEE ranged between 0.98 and 0.995 and 0.089 and 0.180, respectively. The peptides used in this study are available from the AntiJen database (http://www.jenner.ac.uk/AntiJen). The PLS method is available commercially in the SYBYL molecular modeling software package. The resulting models, which can be used for accurate T-cell epitope prediction, will be made freely available online (http://www.jenner.ac.uk/MHCPred).

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Section: Systems and Methodsmentioning

confidence: 99%

Toward Prediction of Class II Mouse Major Histocompatibility Complex Peptide Binding Affinity: in Silico Bioinformatic Evaluation Using Partial Least Squares, a Robust Multivariate Statistical Technique

Hattotuwagama

Toseland

Guan

et al. 2005

J. Chem. Inf. Model.

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“…HSP65 is obviously a prominent mycobacterial antigen. It exhibits several highly immunogenic regions [30,31]. According to our results, multiple MMPs seem to be capable of generating the peptides that span the highly immunogenic 3–13 region.…”

Section: Discussionmentioning

confidence: 82%

“…The capsule (an outer layer of the cell wall) modulates interactions of M. tuberculosis with host macrophages. Mycobacterial HSP65, a portion of which is associated with the capsule [28], plays an important, though incompletely understood, role in these interactions [28–32]. It is not clear if an intracapsular pool of HSP65 results because of the re‐binding of the released cellular HSP65 or because of the specific trafficking of HSP65 to the bacterial surface.…”

Section: Discussionmentioning

confidence: 99%

Matrix metalloproteinase proteolysis of the mycobacterial HSP65 protein as a potential source of immunogenic peptides in human tuberculosis

et al. 2011

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Mycobacterium tuberculosis is the causative agent of human tuberculosis (TB). Mycobacterial secretory protein ESAT-6 induces MMP-9 in epithelial cells neighboring infected macrophages. MMP-9 then enhances recruitment of uninfected macrophages, which contribute to nascent granuloma maturation and bacterial growth. Disruption of MMP-9 function attenuates granuloma formation and bacterial growth. The abundant mycobacterial HSP65 chaperone is the major target for immune response and a critical component in M. tuberculosis adhesion to macrophages. We hypothesized that HSP65 is susceptible to MMP-9 proteolysis and that the resulting HSP65 immunogenic peptides affect host adaptive immunity. To identify MMPs which cleave HSP65, we used the MMP-2 and MMP-9 gelatinases, the simple hemopexin domain MMP-8, the membrane associated MMP-14, MMP-15, MMP-16 and MMP-24, and the glycosylphosphatidylinositol-linked MMP-17 and MMP-25 in our studies. We determined both the relative cleavage efficiency of MMPs against the HSP65 substrate and the peptide sequence of the cleavage sites. Cleavage of the unstructured PAGHG474L C-terminal region initiates the degradation of HSP65 by MMPs. This initial cleavage destroys the substrate-binding capacity of the HSP65 chaperone. Multiple additional cleavages of the unfolded HSP65 then follows. MMP-2, MMP-8, MMP-14, MMP-15 and MMP-16, in addition to MMP-9, generate the known highly immunogenic N-terminal peptide of HSP65. Based on our biochemical data, we now suspect that MMP proteolysis of HSP65 in vivo, including MMP-9 proteolysis, also results in the abundant generation of the N-terminal immunogenic peptide and that this peptide, in addition to intact HSP65, contributes to the complex immunomodulatory interplay in the course of TB infection.

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Identification of T Cell Epitopes of Mycobacterium tuberculosis with Biolistic DNA Vaccination

Nagata

Koide

2012

Methods in Molecular Biology

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Tuberculosis (TB) has been listed as one of the most prevalent and serious infectious diseases worldwide. The etiological pathogen of TB is Mycobacterium tuberculosis (Mtb), a facultative intracellular bacterium. Mycobacterium bovis bacillus Calmette-Guérin (BCG) is the only approved vaccine against TB to date. BCG has been widely used, but the efficacy is questionable, especially in adult pulmonary TB. Therefore, more effective, safe and reliable TB vaccines have been urgently needed. T cell-mediated cellular immune response is a key immune response for effective protective immunity against TB. DNA vaccines using Mtb antigens have been studied as promising future TB vaccines. Most TB DNA vaccine studies so far reported used intramuscular or intradermal injection with needles, as these methods tend to induce a type 1 helper T lymphocyte (Th1)-type immune response that is critical for the protective immunity. We have been using DNA vaccines with gene gun bombardment for T cell epitope identification of various Mtb antigens. We show here our strategy to identify precise Mtb T cell epitopes using DNA vaccines with gene gun bombardment.

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Identification of an I‐A^d restricted peptide on the 65‐kilodalton heat shock protein of Mycobacterium avium

Cited by 4 publications

References 40 publications

Toward Prediction of Class II Mouse Major Histocompatibility Complex Peptide Binding Affinity: in Silico Bioinformatic Evaluation Using Partial Least Squares, a Robust Multivariate Statistical Technique

Toward Prediction of Class II Mouse Major Histocompatibility Complex Peptide Binding Affinity: in Silico Bioinformatic Evaluation Using Partial Least Squares, a Robust Multivariate Statistical Technique

Matrix metalloproteinase proteolysis of the mycobacterial HSP65 protein as a potential source of immunogenic peptides in human tuberculosis

Identification of T Cell Epitopes of Mycobacterium tuberculosis with Biolistic DNA Vaccination

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Identification of an I‐Ad restricted peptide on the 65‐kilodalton heat shock protein of Mycobacterium avium

Cited by 4 publications

References 40 publications

Toward Prediction of Class II Mouse Major Histocompatibility Complex Peptide Binding Affinity: in Silico Bioinformatic Evaluation Using Partial Least Squares, a Robust Multivariate Statistical Technique

Toward Prediction of Class II Mouse Major Histocompatibility Complex Peptide Binding Affinity: in Silico Bioinformatic Evaluation Using Partial Least Squares, a Robust Multivariate Statistical Technique

Matrix metalloproteinase proteolysis of the mycobacterial HSP65 protein as a potential source of immunogenic peptides in human tuberculosis

Identification of T Cell Epitopes of Mycobacterium tuberculosis with Biolistic DNA Vaccination

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Identification of an I‐A^d restricted peptide on the 65‐kilodalton heat shock protein of Mycobacterium avium