Immunoinformatic approach for identification of potential epitopes against Stenotrophomonas maltophilia: A global opportunistic pathogen.

2020 ◽  
Vol 17 ◽  
Author(s):  
R. B. Pragathi ◽  
Shobana Sugumar
Keyword(s):  
Mhc Class I ◽  
Stenotrophomonas Maltophilia ◽  
Pathogenic Bacteria ◽  
Opportunistic Pathogen ◽  
Class I ◽  
High Morbidity ◽  
Population Coverage ◽  
Adhesion Properties

Background: Stenotrophomonas maltophilia is an aerobic, non-fermentative, gram-negative, multidrug-resistant, an opportunistic nosocomial pathogen. It is associated with high morbidity and mortality in severely immunocompromised pediatric patients, including neonates. Immunoinformatic analysis paved a new way to design epitope-based vaccines, which results in a potential immunogen at a lower cost, specific immunity, easy to produce, devoid of side effects, less time consuming than conventional vaccines. To date, there is no development of vaccines or antibody-based treatments for S. maltophilia-associated infections. Introduction: Currently, epitope-based peptide vaccines against pathogenic bacteria have grasped more attention. In our present study, we have utilized various immunoinformatic tools to find a significant epitope that interacts with the maximum number of HLA alleles and the maximum population coverage for developing a vaccine against Stenotrophomonas maltophilia. Methods: This study has incorporated an immunoinformatic based screening approach to explore potential epitope-based vaccine candidates in Stenotrophomonas maltophilia proteome. In this study, 4365 proteins of the Stenotrophomonas maltophilia K279a proteome were screened to identify potential antigens and could be used as the right candidate for the vaccine. Various immunoinformatic tools were used to predict the binding of the promiscuous epitopes with Major Histocompatibility Complex (MHC) class I molecules. Other properties such as allergenicity, physiochemical, adhesion properties, antigenicity, population coverage, epitope conservancy, and toxicity were analyzed for the predicted epitope. Results: This study helps in finding the major epitope in Stenotrophomonas infections. Hence the main objective in this research was to screen complete Stenotrophomonas maltophilia proteome to recognize putative epitope candidates for vaccine design. Using computational vaccinology, immunoinformatic tools approach, and several aspects are obligatory to be fulfilled by an epitope to consider as a vaccine candidate. Our findings were promising and showed that the predicted epitopes were non-allergenic and fulfilled the other parameters required for a suitable candidate based on specific physiochemical, antigenic, and adhesion properties. Conclusion: The epitopes LLFVLCWPL and KSGEGKCGA have shown the highest binding score of −103 and −78.1 kcal/mol with HLA-A*0201 and HLA-B*0702 MHC class I allele, respectively. They were also predicted to be immunogenic and non-allergen. Further various immunological tests both in vivo and in vitro methods to be performed for finding the efficiency of the predicted epitope in the development of a targeted vaccine against Stenotrophomonas maltophilia infection.

scholarly journals Immunotherapy of a murine tumor with interleukin 2. Increased sensitivity after MHC class I gene transfection.

1987 ◽  
Vol 166 (6) ◽  
pp. 1716-1733 ◽  
Author(s):  
J S Weber ◽  
G Jay ◽  
K Tanaka ◽  
S A Rosenberg
Keyword(s):  
T Cells ◽  
Mhc Class I ◽  
Interleukin 2 ◽  
Class I ◽  
High Dose ◽  
Class I Mhc ◽  
High Doses ◽  
I Gene

We have shown that two weakly immunogenic MCA sarcomas developed in our laboratory that are sensitive to high-dose IL-2 immunotherapy express class I MHC in vivo and in vitro. Two nonimmunogenic MCA sarcomas are relatively insensitive to IL-2 therapy and express minimal or no class I MHC molecules in vivo and in vitro. To study the role of MHC in the therapy of tumors with IL-2, a class I-deficient murine melanoma, B16BL6, was transfected with the Kb class I gene. Expression of class I MHC rendered B16BL6 advanced pulmonary macrometastases sensitive to IL-2 immunotherapy. 3-d micrometastases of CL8-2, a class I transfected clone of B16BL6, were significantly more sensitive to IL-2 therapy than a control nontransfected line. Expression of Iak, a class II MHC molecule, had no effect on IL-2 therapy of transfectant pulmonary micrometastases in F1 mice. By using lymphocyte subset depletion with mAbs directed against Lyt-2, therapy of class I transfectant macrometastases with high-dose IL-2 was shown to involve an Lyt-2 cell. In contrast, regression of micrometastases treated with low-dose IL-2 involved Lyt-2+ cells, but regression mediated by high doses of IL-2 did not. We hypothesize that both LAK and Lyt-2+ T cells effect IL-2-mediated elimination of micrometastases, but only Lyt-2+ T cells are involved in macrometastatic regression. Low doses of IL-2 stimulate Lyt-2+ cells to eliminate class I-expressing micrometastases, but high doses of IL-2 can recruit LAK cells to mediate regression of micrometastases independent of class I expression. Only high-dose IL-2, mediating its effect predominantly via Lyt-2+ cells, is capable of impacting on MHC class I-expressing macrometastases. Macrometastases devoid of class I MHC antigens appear to be resistant to IL-2 therapy.

Soluble donor MHC class I antigen inhibits immunologic priming in vitro and in vivo

1998 ◽  
Vol 11 (7) ◽  
pp. S357-S360 ◽  
Author(s):  
E. K. Geissler ◽  
M. N. Scherer ◽  
C. Graeb
Keyword(s):  
Mhc Class I ◽  
Class I ◽  
Mhc Class I Antigen

scholarly journals Potential Immunocompetence of Proteolytic Fragments Produced by Proteasomes before Evolution of the Vertebrate Immune System

1997 ◽  
Vol 186 (2) ◽  
pp. 209-220 ◽  
Author(s):  
Gabriele Niedermann ◽  
Rudolf Grimm ◽  
Elke Geier ◽  
Martina Maurer ◽  
Claudio Realini ◽  
...  
Keyword(s):  
Immune System ◽  
Mhc Class I ◽  
Structural Features ◽  
Interferon Γ ◽  
Class I ◽  
Direct Products ◽  
Vertebrate Immune System ◽  
Mhc Class I Molecules

To generate peptides for presentation by major histocompatibility complex (MHC) class I molecules to T lymphocytes, the immune system of vertebrates has recruited the proteasomes, phylogenetically ancient multicatalytic high molecular weight endoproteases. We have previously shown that many of the proteolytic fragments generated by vertebrate proteasomes have structural features in common with peptides eluted from MHC class I molecules, suggesting that many MHC class I ligands are direct products of proteasomal proteolysis. Here, we report that the processing of polypeptides by proteasomes is conserved in evolution, not only among vertebrate species, but including invertebrate eukaryotes such as insects and yeast. Unexpectedly, we found that several high copy ligands of MHC class I molecules, in particular, self-ligands, are major products in digests of source polypeptides by invertebrate proteasomes. Moreover, many major dual cleavage peptides produced by invertebrate proteasomes have the length and the NH2 and COOH termini preferred by MHC class I. Thus, the ability of proteasomes to generate potentially immunocompetent peptides evolved well before the vertebrate immune system. We demonstrate with polypeptide substrates that interferon γ induction in vivo or addition of recombinant proteasome activator 28α in vitro alters proteasomal proteolysis in such a way that the generation of peptides with the structural features of MHC class I ligands is optimized. However, these changes are quantitative and do not confer qualitatively novel characteristics to proteasomal proteolysis. The data suggest that proteasomes may have influenced the evolution of MHC class I molecules.

scholarly journals The Immunoevasive Function Encoded by the Mouse Cytomegalovirus Gene m152 Protects the Virus against T Cell Control in Vivo

1999 ◽  
Vol 190 (9) ◽  
pp. 1285-1296 ◽  
Author(s):  
Astrid Krmpotic ◽  
Martin Messerle ◽  
Irena Crnkovic-Mertens ◽  
Bojan Polic ◽  
Stipan Jonjic ◽  
...  
Keyword(s):  
Mhc Class I ◽  
Gene Function ◽  
Class I ◽  
Viral Gene ◽  
Mouse Cytomegalovirus ◽  
Mcmv Infection ◽  
Golgi Compartment ◽  
Intermediate Compartment

Cytomegaloviruses encode numerous functions that inhibit antigen presentation in the major histocompatibility complex (MHC) class I pathway in vitro. One example is the mouse cytomegalovirus (MCMV) glycoprotein gp40, encoded by the m152 gene, which selectively retains murine but not human MHC class I complexes in the endoplasmic reticulum–Golgi intermediate compartment/cis-Golgi compartment (Ziegler, H., R. Thäle, P. Lucin, W. Muranyi, T. Flohr, H. Hengel, H. Farrell, W. Rawlinson, and U.H. Koszinowski. 1997. Immunity. 6:57–66). To investigate the in vivo significance of this gene function during MCMV infection of the natural host, we constructed recombinants of MCMV in which the m152 gene was deleted, as were the corresponding virus revertants. We report on the following findings: Deletion of the m152 gene has no effect on virus replication in cell culture, whereas after infection of mice, the m152-deficient virus replicates to significantly lower virus titers. This attenuating effect is lifted by reinsertion of the gene into the mutant. Mutants and revertants grow to the same titer in animals deprived of the function targeted by the viral gene function, namely in mice deficient in β2-microglobulin, mice deficient in the CD8 molecule, and mice depleted of T cells. Upon adoptive transfer of naive lymphocytes into infected mice, the absence of the m152 gene function sensitizes the virus to primary lymphocyte control. These results prove that MHC-reactive functions protect CMVs against attack by CD8+ T lymphocytes in vivo.

Expansion of CD8+ Cytotoxic T Cells in vitro and in vivo Using MHC Class I Tetramers

Tumor Biology ◽  
2007 ◽  
Vol 28 (2) ◽  
pp. 70-76 ◽  
Author(s):  
Philip Savage ◽  
Maggie Millrain ◽  
Sofia Dimakou ◽  
Justin Stebbing ◽  
Julian Dyson
Keyword(s):  
T Cells ◽  
Mhc Class I ◽  
Cytotoxic T Cells ◽  
Class I

Occupancy of upstream regulatory sites in vivo coincides with major histocompatibility complex class I gene expression in mouse tissues

1992 ◽  
Vol 12 (8) ◽  
pp. 3590-3599
Author(s):  
A Dey ◽  
A M Thornton ◽  
M Lonergan ◽  
S M Weissman ◽  
J W Chamberlain ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Mhc Class I ◽  
Class I ◽  
Interferon Response ◽  
Upstream Region ◽  
Response Element ◽  
Tissue Specific ◽  
Histocompatibility Complex

The major histocompatibility complex (MHC) class I HLA-B7 transgene carrying a 660-bp upstream sequence is expressed in the mouse with tissue specificity that parallels that of the expression of endogenous mouse MHC class I (H-2) genes. We have performed in vivo genomic footprinting for the HLA-B7 transgene and the endogenous H-2Kb gene. We show that the upstream region of both the transgene and the endogenous gene was extensively occupied in spleen tissue, where these genes are expressed at high levels. In contrast, no occupancy was detected in brain tissue, where expression of these genes is virtually absent. Sites exhibiting in vivo protection correspond to cis elements previously shown to bind to nuclear factors in vitro, including the constitutive enhancer region I and the interferon response element. The strongest tissue-specific protection was detected at site alpha, located downstream from the interferon response element. Site alpha bound a constitutively expressed nuclear factor(s) in vitro that exhibited an overlapping specificity which may involve a nuclear hormone receptor, RXR, and an AP-1-related factor. Site alpha was functional in vivo, as it enhanced MHC class I transcription in lymphocytes. These results show that the tissue-specific occupancy of the MHC class I regulatory sequences in vivo correlates with their expression and suggest that in vivo occupancy is controlled by a mechanism other than the mere presence of factors capable of binding to these sites. Our results suggest that a sequence present in the 660-bp upstream region in a human leukocyte antigen gene directs tissue-specific occupancy of MHC class I genes in vivo, independently of their position and copy number, illustrating a potential advantage of using a transgene for delimitation of the sequence requirement for in vivo occupancy.

scholarly journals In vivo and in vitro immunogenicity of novel MHC class I presented epitopes to confer protective immunity against chronic HTLV-1 infection

Vaccine ◽  
2018 ◽  
Vol 36 (33) ◽  
pp. 5046-5057 ◽  
Author(s):  
Ria Mulherkar ◽  
Aykan Karabudak ◽  
Rashida Ginwala ◽  
Xiaofang Huang ◽  
Aileen Rowan ◽  
...  
Keyword(s):  
Mhc Class I ◽  
Protective Immunity ◽  
Class I

Engraftment of C6-2B Cells into the Striatum of Aci Nude Rats as a Tool for Comparison of the in Vitro and in Vivo Phenotype of a Glioma Cell Line

1997 ◽  
Vol 6 (3) ◽  
pp. 317-326 ◽  
Author(s):  
Carlo Tornatore ◽  
Stuart Rabin ◽  
Belinda Baker-Cairns ◽  
Stuart Keir ◽  
Italo Mocchetti
Keyword(s):  
Inflammatory Response ◽  
Cell Line ◽  
Mhc Class I ◽  
Glioma Cell ◽  
Glioma Cell Line ◽  
Class I ◽  
Class I Mhc ◽  
Nude Rats

The C6-2B is a well-characterized glioma cell line used extensively in the study of malignant glial biology. While the C6-2B cell line has traditionally been thought of as a homogenous cell line, the in vitro phenotype of the C6-2B cell line can vary considerably depending on the culture technique used and the stratum on which the cells are grown. Thus, we asked whether the in vitro phenotype of the C6-2B cell line was significantly different than the in vivo phenotype of the cell line once it was engrafted into the striatum of nude rats. Under culture conditions used in our laboratory, 100% of the C6 cells were found to express p75, the low-affinity nerve growth factor (NGF) receptor, and Major Histocompatability Class I (MHC Class I), while only 10-15% demonstrated vimentin reactivity. Immunohistochemistry was consistently negative for GFAP, trkA (the high-affinity receptor for NGF), CD4, CD8, and a macrophage specific marker (Ox-41). Once engrafted into the striatum of nude rats, the cells remained 100% p75 and MHC Class I positive, and again, only 15% of the cells demonstrated vimentin reactivity. The grafted cells retained this characteristic for 28 days in vivo. Although an immunoincompetent host was selected to minimize the effects an inflammatory response would have on the graft, a transient inflammatory response was detected. During the first week of engraftment, numerous MHC class II cells, some of which were macrophages, were seen infiltrating the graft. However, by 4 weeks postengraftment, no inflammatory cells were appreciated in the graft and surprisingly little reactive gliosis was seen in the penumbra of the tumor mass. Thus, the limited number of in vitro phe-notypic characteristics we examined in the C6-2B cell line remained constant once the cells were engrafted into the striatum of athymic nude rats.

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