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Definition of CD4 Immunosignatures Associated with MTB

We have recently described the first true genome-wide screen for CD4(+) T-cell reactivity directed against Mycobacterium tuberculosis (MTB) in latent TB-infected individuals. The approach relied on predictions of HLA-binding capacity for a panel of DR, DP, and DQ alleles representative of those most...

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Autores principales: Lindestam Arlehamn, Cecilia S., Sette, Alessandro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3970006/
https://www.ncbi.nlm.nih.gov/pubmed/24715893
http://dx.doi.org/10.3389/fimmu.2014.00124
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author Lindestam Arlehamn, Cecilia S.
Sette, Alessandro
author_facet Lindestam Arlehamn, Cecilia S.
Sette, Alessandro
author_sort Lindestam Arlehamn, Cecilia S.
collection PubMed
description We have recently described the first true genome-wide screen for CD4(+) T-cell reactivity directed against Mycobacterium tuberculosis (MTB) in latent TB-infected individuals. The approach relied on predictions of HLA-binding capacity for a panel of DR, DP, and DQ alleles representative of those most commonly expressed in the general population, coupled with high throughput ELISPOT assays. The results identified hundreds of novel epitopes and antigens, and documented the novel observation that T cells in latent MTB infection are confined to the CXCR3(+)CCR6(+) phenotype and largely directed against three antigenic “islands” within the MTB genome. In parallel, we have made generally available to the scientific community the technical approaches and reagents developed in the process, such as motifs, algorithms, and binding assays for several common HLA class II alleles, and a panel of single allele HLA class II transfected cell lines representative of the most frequent specificities in the general population. Recent efforts have been focused on characterization of epitopes and antigens recognized by patients with active TB and individuals vaccinated with BCG, with the aim of providing the first systematic evaluation of the overlap between latent, active, and BCG cohorts. The definition of a broad range of epitopes restricted by common HLA molecules, will facilitate development of diagnostic reagents, allow a rigorous evaluation of T-cell responses associated with TB infection in humans, and enable the evaluation of the immunogenicity of different vaccine candidates. Furthermore, it might suggest new candidates for vaccine and diagnostic development.
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spelling pubmed-39700062014-04-08 Definition of CD4 Immunosignatures Associated with MTB Lindestam Arlehamn, Cecilia S. Sette, Alessandro Front Immunol Immunology We have recently described the first true genome-wide screen for CD4(+) T-cell reactivity directed against Mycobacterium tuberculosis (MTB) in latent TB-infected individuals. The approach relied on predictions of HLA-binding capacity for a panel of DR, DP, and DQ alleles representative of those most commonly expressed in the general population, coupled with high throughput ELISPOT assays. The results identified hundreds of novel epitopes and antigens, and documented the novel observation that T cells in latent MTB infection are confined to the CXCR3(+)CCR6(+) phenotype and largely directed against three antigenic “islands” within the MTB genome. In parallel, we have made generally available to the scientific community the technical approaches and reagents developed in the process, such as motifs, algorithms, and binding assays for several common HLA class II alleles, and a panel of single allele HLA class II transfected cell lines representative of the most frequent specificities in the general population. Recent efforts have been focused on characterization of epitopes and antigens recognized by patients with active TB and individuals vaccinated with BCG, with the aim of providing the first systematic evaluation of the overlap between latent, active, and BCG cohorts. The definition of a broad range of epitopes restricted by common HLA molecules, will facilitate development of diagnostic reagents, allow a rigorous evaluation of T-cell responses associated with TB infection in humans, and enable the evaluation of the immunogenicity of different vaccine candidates. Furthermore, it might suggest new candidates for vaccine and diagnostic development. Frontiers Media S.A. 2014-03-24 /pmc/articles/PMC3970006/ /pubmed/24715893 http://dx.doi.org/10.3389/fimmu.2014.00124 Text en Copyright © 2014 Lindestam Arlehamn and Sette. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Lindestam Arlehamn, Cecilia S.
Sette, Alessandro
Definition of CD4 Immunosignatures Associated with MTB
title Definition of CD4 Immunosignatures Associated with MTB
title_full Definition of CD4 Immunosignatures Associated with MTB
title_fullStr Definition of CD4 Immunosignatures Associated with MTB
title_full_unstemmed Definition of CD4 Immunosignatures Associated with MTB
title_short Definition of CD4 Immunosignatures Associated with MTB
title_sort definition of cd4 immunosignatures associated with mtb
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3970006/
https://www.ncbi.nlm.nih.gov/pubmed/24715893
http://dx.doi.org/10.3389/fimmu.2014.00124
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