A simple assay to quantify mycobacterial lipid antigen-specific T cell receptors in human tissues and blood.
PLoS Negl Trop Dis
; 15(12): e0010018, 2021 12.
Article
em En
| MEDLINE
| ID: mdl-34914694
ABSTRACT
T cell receptors (TCRs) encode the history of antigenic challenge within an individual and have the potential to serve as molecular markers of infection. In addition to peptide antigens bound to highly polymorphic MHC molecules, T cells have also evolved to recognize bacterial lipids when bound to non-polymorphic CD1 molecules. One such subset, germline-encoded, mycolyl lipid-reactive (GEM) T cells, recognizes mycobacterial cell wall lipids and expresses a conserved TCR-É chain that is shared among genetically unrelated individuals. We developed a quantitative PCR assay to determine expression of the GEM TCR-É nucleotide sequence in human tissues and blood. This assay was validated on plasmids and T cell lines. We tested blood samples from South African subjects with or without tuberculin reactivity or with active tuberculosis disease. We were able to detect GEM TCR-É above the limit of detection in 92% of donors but found no difference in GEM TCR-É expression among the three groups after normalizing for total TCR-É expression. In a cohort of leprosy patients from Nepal, we successfully detected GEM TCR-É in 100% of skin biopsies with histologically confirmed tuberculoid and lepromatous leprosy. Thus, GEM T cells constitute part of the T cell repertoire in the skin. However, GEM TCR-É expression was not different between leprosy patients and control subjects after normalization. Further, these results reveal the feasibility of developing a simple, field deployable molecular diagnostic based on mycobacterial lipid antigen-specific TCR sequences that are readily detectable in human tissues and blood independent of genetic background.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Contexto em Saúde:
2_ODS3
/
3_ND
Problema de saúde:
2_enfermedades_transmissibles
/
3_leprosy
/
3_neglected_diseases
/
3_tuberculosis
Assunto principal:
Tuberculose
/
Receptores de Antígenos de Linfócitos T alfa-beta
/
Técnicas de Diagnóstico Molecular
/
Hanseníase
/
Lipídeos
/
Mycobacterium
Tipo de estudo:
Diagnostic_studies
/
Etiology_studies
/
Evaluation_studies
/
Incidence_studies
/
Observational_studies
/
Risk_factors_studies
Limite:
Humans
País/Região como assunto:
Africa
/
Asia
Idioma:
En
Revista:
PLoS Negl Trop Dis
Assunto da revista:
MEDICINA TROPICAL
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos