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Sundaramurthi J.C.,National Institute for Research in Tuberculosis | Ramanathan V.D.,National Institute for Research in Tuberculosis Formerly Tuberculosis Research Center | Hanna L.E.,National Institute for Research in Tuberculosis
AIDS Research and Human Retroviruses | Year: 2013

HLA-B*27:05 is one of the widely reported alleles associated with resistance to HIV, while HLA-A24, HLA-B7, HLA-B*07:02, HLA-B*35:01, HLA-B*53:01, and HLA-B40 are reported to be associated with susceptibility to HIV. Using a bioinformatics approach we attempted to predict potential HLA-B*27:05-specific HIV-1C epitopes that do not bind to susceptibility-associated HLA alleles based on our hypothesis that such epitopes have a greater probability of eliciting a protective immune response in the host. A consensus sequence was built for all proteins of Indian clade C virus. Epitopes specific to HLA-B*27:05 were predicted from the consensus sequence using two different bioinformatics methods to enhance the accuracy of the prediction. Epitopes that were also predicted to bind to any of the susceptibility-associated HLA alleles were excluded from the list. The short-listed epitopes were modeled using MODPROPEP to refine the prediction. Fourteen peptides were identified as epitopes by both sequence-based methods and were found to interact strongly with HLA-B*27:05 by molecular modeling studies. Five of the 14 epitopes were previously reported as immunogenic by other researchers, while the remaining nine are novel. The 14 epitopes have been repeatedly identified by three different methods indicating their potential as useful candidates for an effective HIV vaccine. © Copyright 2013, Mary Ann Liebert, Inc. 2013. Source


Harishankar M.,National Institute for Research in Tuberculosis Formerly Tuberculosis Research Center | Selvaraj P.,National Institute for Research in Tuberculosis Formerly Tuberculosis Research Center
Human Immunology | Year: 2016

Vitamin D receptor (VDR) gene variants have been shown to be regulating the immune response in tuberculosis. We studied the regulatory role of VDR promoter Cdx-2 and 3'UTR TaqI gene variants on chemokine levels from culture filtrate antigen (CFA) stimulated with or without 1,25(OH)2D3 treated peripheral blood mononuclear cells of 50 pulmonary tuberculosis patients (PTB) and 51 normal healthy controls (HCs). In CFA with 1,25(OH)2D3 treated cultures, the MIP-1α, MIP-1β, RANTES levels were significantly decreased in Cdx-2 AA genotype compared to GG genotype, while a significantly increased MIG level was observed in Cdx-2 AA genotype (p<0.05). In TaqI polymorphism, tt genotype significantly decreased MIP-1β and RANTES levels compared to TT genotype. Moreover, a significantly increased level of IP-10 and MIG was observed in TaqI tt genotype compared with TT genotype (p<0.05). The results suggests that the 1,25(OH)2D3 may alter the chemokine response through the VDR polymorphic variants during infection. © 2016. Source


Harishankar M.,National Institute for Research in Tuberculosis Formerly Tuberculosis Research Center | Afsal K.,National Institute for Research in Tuberculosis Formerly Tuberculosis Research Center | Banurekha V.V.,National Institute for Research in Tuberculosis Formerly Tuberculosis Research Center | Meenakshi N.,Institute of Thoracic Medicine | Selvaraj P.,National Institute for Research in Tuberculosis Formerly Tuberculosis Research Center
International Immunopharmacology | Year: 2014

1,25-Dihydroxy vitamin D3[1,25(OH)2D3] is a potent immunomodulator and regulates various immune responses to Mycobacterium tuberculosis (Mtb). The present study aimed to understand the effect of 1,25(OH)2D3on pro-inflammatory cytokine response to Mtb antigen. Peripheral blood mononuclear cells from 42 healthy controls (HCs) and 42 pulmonary tuberculosis (PTB) patients were cultured with culture filtrate antigen (CFA) of Mtb with and without 1,25(OH)2D3at 10- 7M concentration for 72 h. The levels of IL-1α, IL-1β, TNF-α, TNF-β, IL-17 and IL-23 were estimated in the culture supernatants by ELISA. 1,25(OH)2D3significantly suppressed all the CFA induced pro-inflammatory cytokines (p < 0.05) studied except IL-1β in both HCs and PTB patients. Among the PTB patients, the observed suppression was visible both in patients with and without cavitary tuberculosis. The present study results suggest that 1,25(OH)2D3downregulates the production of pro-inflammatory cytokines and may control the exacerbated inflammatory response that may protect the host from excessive tissue damage at the site of infection. © 2014 Elsevier B.V. Source


Harishankar M.,National Institute for Research in Tuberculosis Formerly Tuberculosis Research Center | Anbalagan S.,National Institute for Research in Tuberculosis Formerly Tuberculosis Research Center | Selvaraj P.,National Institute for Research in Tuberculosis Formerly Tuberculosis Research Center
International Immunopharmacology | Year: 2016

1,25-DihydroxyVitamin D3 [1,25(OH)2D3] the active form of Vitamin D3 acts as an immunomodulator in various immune cells. The present study is aimed to study the effect of 1,25(OH)2D3 on chemokine levels and regulatory T-cells in 51 healthy controls (HCs) and 50 pulmonary tuberculosis (PTB) patients. Peripheral blood mononuclear cells were cultured with culture filtrate antigen (CFA) of Mycobacterium tuberculosis in the presence or absence of 1,25(OH)2D3 at 10- 7 M concentration for 72 h and the percentage positive regulatory T-cell subsets were studied using flow cytometry. The chemokine levels were estimated in the culture supernatants by ELISA. 1,25(OH)2D3 significantly upregulated the frequency of regulatory T-cell subsets while suppressed the production of chemokine levels in CFA stimulated cultures of HCs and PTB patients (p < 0.05). Correlation analysis revealed a significant negative correlation between CD4 + Foxp3 + regulatory T-cells and MCP-1, MIP-1β and IP-10 in CFA stimulated with 1,25(OH)2D3 treated cells (p < 0.05). The results suggested that 1,25(OH)2D3 upregulated regulatory T-cells and act as anti-inflammatory by downregulating chemokine levels which could be beneficial to protect the host from inflammation and tissue damage during infection. © 2016 Published by Elsevier B.V. Source


Sundaramurthi J.C.,National Institute for Research in Tuberculosis Formerly Tuberculosis Research Center | Swaminathan S.,National Institute for Research in Tuberculosis Formerly Tuberculosis Research Center | Hanna L.E.,National Institute for Research in Tuberculosis Formerly Tuberculosis Research Center
Immunogenetics | Year: 2012

Earlier studies have identified a large number of immunogenic epitopes in HIV-1. Efforts are required to prioritize these epitopes in order to identify the best candidates for formulating an effective multi-epitope vaccine for HIV. We modeled 155 known cytotoxic T lymphocyte epit-opes of HIV-1 subtype C on the 3D structure of HLA-A *0201, HLA-B *2705, and HLA-B *5101 using MOD-PROPEP, as these alleles are known to be associated with resistance to HIV/slow progression to AIDS. Thirty-six epitopes were identified to bind to all the three HLA alleles with better binding affinity than the control peptides com-plexed with each HLA allele but not to any of the HLA alleles reported to be associated with susceptibility to HIV infection/rapid progression to disease. As increase in stability of the epitope-HLA complex results in increased immu-nogenicity, the short-listed epitopes could be suitable candidates for vaccine development. Twenty of the 36 epit-opes were polyfunctional in nature adding to their immuno-logical relevance for vaccine design. Further, 9 of the 20 polyfunctional epitopes were found to bind to all three resistance-associated HLA alleles using an additional method, adding worth to their potential as candidates for a vaccine formulation for HIV-1C. © Springer-Verlag 2012. Source

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