scholarly journals Mimicking B and T cell epitopes between Mycobacterium leprae and host as predictive biomarkers in type 1 reaction in leprosy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Vinay Kumar Pathak ◽  
Itu Singh ◽  
Shoor Vir Singh ◽  
Utpal Sengupta
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Basic Protein ◽  
Predictive Biomarkers ◽  
Mycobacterium Leprae ◽  
Autoimmune Response ◽  
T Cell Epitopes ◽  
Leprosy Patients

AbstractSeveral Mycobacterial infections including leprosy and tuberculosis are known to evoke autoimmune responses by modulating homeostatic mechanism of the host. Presence of autoantibodies like, rheumatoid factor, anti-nuclear factor and antibodies to host, collagen, keratin, myelin basic protein (MBP) and myosin, have been earlier reported in leprosy patients. In the present study, we detected the role of mimicking epitopes between Mycobacterium leprae and host components in the induction of autoimmune response in leprosy. Based on our previous findings, we predicted and synthesized a total of 15 mimicking linear B cell epitopes (BCE) and 9 mimicking linear T cell epitopes (TCE) of keratin and MBP. Humoral and cell-mediated immune responses against these epitopes were investigated in Non-reaction (NR), Type 1 reaction (T1R) leprosy patients, and healthy controls. We observed significantly higher levels of antibodies against 8 BCE in T1R in comparison to NR leprosy patients. Further, we also found 5 TCE significantly associated with lymphocyte proliferation in the T1R group. Our results indicated that these epitopes play a key role in the induction of autoimmune response in leprosy and are also strongly associated with the inflammatory episodes of T1R. Conclusively, these molecules may be employed as a biomarker to predict the inflammatory episodes of T1R.

scholarly journals Control of Human Immunodeficiency Virus Type 1 Is Associated with HLA-B*13 and Targeting of Multiple Gag-Specific CD8+ T-Cell Epitopes

2007 ◽  
Vol 81 (7) ◽  
pp. 3667-3672 ◽  
Author(s):  
Isobella Honeyborne ◽  
Andrew Prendergast ◽  
Florencia Pereyra ◽  
Alasdair Leslie ◽  
Hayley Crawford ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Cytotoxic T Lymphocyte ◽  
Hla Class I ◽  
T Cell Epitopes ◽  
Immunodeficiency Virus

ABSTRACT To better understand relationships between CD8+ T-cell specificity and the immune control of human immunodeficiency virus type 1 (HIV-1), we analyzed the role of HLA-B*13, an allele associated with low viremia, in a cohort of 578 C clade-infected individuals in Durban, South Africa. Six novel B*13-restricted cytotoxic T lymphocyte epitopes were defined from analyses of 37 B*13-positive subjects, including three Gag epitopes. These B*13-restricted epitopes contribute to a broad Gag-specific CD8+ response that is associated with the control of viremia. These data are consistent with data from studies of other HLA-class I alleles associated with HIV control that have shown that the targeting of multiple Gag epitopes is associated with relative suppression of viremia.

scholarly journals Role of TEFFECTOR/MEMORY Cells, TBX21 Gene Expression and T-Cell Homing Receptor on Type 1 Reaction in Borderline Lepromatous Leprosy Patients

PLoS ONE ◽  
2016 ◽  
Vol 11 (10) ◽  
pp. e0164543 ◽  
Author(s):  
Luciana Nahar dos Santos ◽  
Pedro Henrique Lopes da Silva ◽  
Iris Maria Peixoto Alvim ◽  
José Augusto da Costa Nery ◽  
Flávio Alves Lara ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
Lepromatous Leprosy ◽  
Cell Homing ◽  
Homing Receptor ◽  
Leprosy Patients ◽  
T Cell Homing ◽  
Tbx21 Gene

scholarly journals Protective Immune Responses to a Recombinant Adenovirus Type 35 Tuberculosis Vaccine in Two Mouse Strains: CD4 and CD8 T-Cell Epitope Mapping and Role of Gamma Interferon

2007 ◽  
Vol 75 (8) ◽  
pp. 4105-4115 ◽  
Author(s):  
Katarina Radošević ◽  
Catharina W. Wieland ◽  
Ariane Rodriguez ◽  
Gerrit Jan Weverling ◽  
Ratna Mintardjo ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Epitope Mapping ◽  
Recombinant Adenovirus ◽  
Cd8 T Cell ◽  
Mouse Strains ◽  
T Cell Epitopes ◽  
Cell Responses ◽  
Ifn Γ

ABSTRACT There is an urgent need for an efficacious vaccine against tuberculosis (TB). Cellular immune responses are key to an effective protective response against TB. Recombinant adenovirus (rAd) vectors are especially suited to the induction of strong T-cell immunity and thus represent promising vaccine vehicles for the prevention of TB. We have previously reported on rAd vector serotype 35, the serotype of choice due to low preexisting immunity worldwide, which expresses a unique fusion protein of Mycobacterium tuberculosis antigens Ag85A, Ag85B, and TB10.4 (Ad35-TBS). Here, we demonstrate that Ad35-TBS confers protection against M. tuberculosis when administered to mice through either an intranasal or an intramuscular route. Histological evaluation of lung tissue corroborated the protection and, in addition, demonstrated differences between two mouse strains, with diffuse inflammation in BALB/c mice and distinct granuloma formation in C57BL/6 mice. Epitope mapping analysis in these mouse strains showed that the major T-cell epitopes are conserved in the artificial fusion protein, while three novel CD8 peptides were discovered. Using a defined set of T-cell epitopes, we reveal differences between the two mouse strains in the type of protective immune response, demonstrating that different antigen-specific gamma interferon (IFN-γ)-producing T cells can provide protection against M. tuberculosis challenge. While in BALB/c (H-2d) mice, a dominant CD8 T-cell response was detected, in C57BL/6 (H-2b) mice, more balanced CD4/CD8 T-cell responses were observed, with a more pronounced CD4 response in the lungs. These results unify conflicting reports on the relative importance of CD4 versus CD8 T-cell responses in protection and emphasize the key role of IFN-γ.

High-throughput Screening for CD8+ T Cell Epitopes Targeted in Type 1 Diabetes

2010 ◽  
Vol 135 ◽  
pp. S19
Author(s):  
Brian Hondowicz ◽  
Katharine Schwedhelm ◽  
Arnold Kas ◽  
Michael Tasch ◽  
Nirasha Ramchurren ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
T Cell ◽  
High Throughput ◽  
High Throughput Screening ◽  
Cd8 T Cell ◽  
T Cell Epitopes

scholarly journals Enhanced T- and B-cell responses to simian immunodeficiency virus (SIV)agm, SIVmac and human immunodeficiency virus type 1 Gag DNA immunization and identification of novel T-cell epitopes in mice via codon optimization

2009 ◽  
Vol 90 (10) ◽  
pp. 2513-2518 ◽  
Author(s):  
Christine S. Siegismund ◽  
Oliver Hohn ◽  
Reinhard Kurth ◽  
Stephen Norley
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
B Cell ◽  
Simian Immunodeficiency Virus ◽  
Codon Optimization ◽  
T Cell Epitopes ◽  
Gm Csf ◽  
Cell Responses ◽  
Immunodeficiency Virus

As a prelude to primate studies, the immunogenicity of wild-type and codon-optimized versions of simian immunodeficiency virus (SIV)agm Gag DNA, with and without co-administered granulocyte–macrophage colony-stimulating factor (GM-CSF) DNA, was directly compared in two strains of mice. Gag-specific T cells in the splenocytes of BALB/c and C57BL/6 mice immunized by gene gun were quantified by ELISpot using panels of overlapping synthetic peptides (15mers) spanning the entire capsid proteins of SIVagm, SIVmac and human immunodeficiency virus type 1. Specific antibodies were measured by ELISA. Codon optimization was shown to significantly increase the immune response to the DNA immunogens, reducing the amount of DNA necessary to induce cellular and antibody responses by one and two orders of magnitude, respectively. Co-administration of murine GM-CSF DNA was necessary for the induction of high level T- and B-cell responses. Finally, it was possible to identify both known and novel T-cell epitopes in the Gag proteins of the three viruses.

scholarly journals Comparative Analysis of B- and T-Cell Epitopes of Mycobacterium leprae and Mycobacterium tuberculosis Culture Filtrate Protein 10

2004 ◽  
Vol 72 (6) ◽  
pp. 3161-3170 ◽  
Author(s):  
John S. Spencer ◽  
Hee Jin Kim ◽  
Angela M. Marques ◽  
Mercedes Gonzalez-Juarerro ◽  
Monica C. B. S. Lima ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
T Cell ◽  
Culture Filtrate ◽  
Mycobacterium Leprae ◽  
Cross Reactivity ◽  
Interferon Response ◽  
Positive Staining ◽  
T Cell Epitopes ◽  
Peptide Epitopes ◽  
Culture Filtrate Protein

ABSTRACT Culture filtrate protein 10 (CFP-10) from Mycobacterium tuberculosis is a well-characterized immunodominant 10-kDa protein antigen known to elicit a very potent early gamma interferon response in T cells from M. tuberculosis-infected mice and humans. The sequence of the Mycobacterium leprae homologue of CFP-10 shows only 40% identity (60% homology) at the protein level with M. tuberculosis CFP-10 and thus has the potential for development as a T- or B-cell reactive antigen for specific diagnosis of leprosy. Antisera raised in mice or rabbits against recombinant M. leprae and M. tuberculosis CFP-10 proteins reacted only with homologous peptides from arrays of overlapping synthetic peptides, indicating that there was no detectable cross-reactivity at the antibody level. Sera from leprosy and tuberculosis patients were also specific for the homologous protein or peptides and showed distinct patterns of recognition for either M. leprae or M. tuberculosis CFP-10 peptides. At the cellular level, only 2 of 45 mouse T-cell hybridomas raised against either M. leprae or M. tuberculosis CFP-10 displayed a cross-reactive response against the N-terminal heterologous CFP-10 peptide, the region that exhibits the highest level of identity in the two proteins; however, the majority of peptide epitopes recognized by mouse T-cell hybridomas specific for each protein did not cross-react with heterologous peptides. Coupled with the human serology data, these results raise the possibility that peptides that could be used to differentiate infections caused by these two related microorganisms could be developed. Immunohistochemical staining of sections of M. leprae-infected nude mouse footpads resulted in strongly positive staining in macrophages and dendritic cells, as well as weaker staining in extracellular areas, suggesting that M. leprae CFP-10, like its homologue in M. tuberculosis, is a secreted protein.

Sign in / Sign up

Export Citation Format

Share Document