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CD1b Tetramers Broadly Detect T Cells That Correlate With Mycobacterial Exposure but Not Tuberculosis Disease State
The non-polymorphic nature of CD1 proteins creates a situation in which T cells with invariant T cell receptors (TCRs), like CD1d-specific NKT cells, are present in all humans. CD1b is an abundant protein on human dendritic cells that presents M. tuberculosis (Mtb) lipid antigens to T cells. Analysi...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7033476/ https://www.ncbi.nlm.nih.gov/pubmed/32117314 http://dx.doi.org/10.3389/fimmu.2020.00199 |
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author | Lopez, Kattya Iwany, Sarah K. Suliman, Sara Reijneveld, Josephine F. Ocampo, Tonatiuh A. Jimenez, Judith Calderon, Roger Lecca, Leonid Murray, Megan B. Moody, D. Branch Van Rhijn, Ildiko |
author_facet | Lopez, Kattya Iwany, Sarah K. Suliman, Sara Reijneveld, Josephine F. Ocampo, Tonatiuh A. Jimenez, Judith Calderon, Roger Lecca, Leonid Murray, Megan B. Moody, D. Branch Van Rhijn, Ildiko |
author_sort | Lopez, Kattya |
collection | PubMed |
description | The non-polymorphic nature of CD1 proteins creates a situation in which T cells with invariant T cell receptors (TCRs), like CD1d-specific NKT cells, are present in all humans. CD1b is an abundant protein on human dendritic cells that presents M. tuberculosis (Mtb) lipid antigens to T cells. Analysis of T cell clones suggested that semi-invariant TCRs exist in the CD1b system, but their prevalence in humans is not known. Here we used CD1b tetramers loaded with mycolic acid or glucose monomycolate to study polyclonal T cells from 150 Peruvian subjects. We found that CD1b tetramers loaded with mycolic acid or glucose monomycolate antigens stained TRAV1-2(+) GEM T cells or TRBV4-1(+) LDN5-like T cells in the majority of subjects tested, at rates ~10-fold lower than NKT cells. Thus, GEM T cells and LDN5-like T cells are a normal part of the human immune system. Unlike prior studies measuring MHC- or CD1b-mediated activation, this large-scale tetramer study found no significant differences in rates of CD1b tetramer-mycobacterial lipid staining of T cells among subjects with Mtb exposure, latent Mtb infection or active tuberculosis (TB) disease. In all subjects, including “uninfected” subjects, CD1b tetramer(+) T cells expressed memory markers at high levels. However, among controls with lower mycobacterial antigen exposure in Boston, we found significantly lower frequencies of T cells staining with CD1b tetramers loaded with mycobacterial lipids. These data link CD1b-specific T cell detection to mycobacterial exposure, but not TB disease status, which potentially explains differences in outcomes among CD1-based clinical studies, which used control subjects with low Mtb exposure. |
format | Online Article Text |
id | pubmed-7033476 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-70334762020-02-28 CD1b Tetramers Broadly Detect T Cells That Correlate With Mycobacterial Exposure but Not Tuberculosis Disease State Lopez, Kattya Iwany, Sarah K. Suliman, Sara Reijneveld, Josephine F. Ocampo, Tonatiuh A. Jimenez, Judith Calderon, Roger Lecca, Leonid Murray, Megan B. Moody, D. Branch Van Rhijn, Ildiko Front Immunol Immunology The non-polymorphic nature of CD1 proteins creates a situation in which T cells with invariant T cell receptors (TCRs), like CD1d-specific NKT cells, are present in all humans. CD1b is an abundant protein on human dendritic cells that presents M. tuberculosis (Mtb) lipid antigens to T cells. Analysis of T cell clones suggested that semi-invariant TCRs exist in the CD1b system, but their prevalence in humans is not known. Here we used CD1b tetramers loaded with mycolic acid or glucose monomycolate to study polyclonal T cells from 150 Peruvian subjects. We found that CD1b tetramers loaded with mycolic acid or glucose monomycolate antigens stained TRAV1-2(+) GEM T cells or TRBV4-1(+) LDN5-like T cells in the majority of subjects tested, at rates ~10-fold lower than NKT cells. Thus, GEM T cells and LDN5-like T cells are a normal part of the human immune system. Unlike prior studies measuring MHC- or CD1b-mediated activation, this large-scale tetramer study found no significant differences in rates of CD1b tetramer-mycobacterial lipid staining of T cells among subjects with Mtb exposure, latent Mtb infection or active tuberculosis (TB) disease. In all subjects, including “uninfected” subjects, CD1b tetramer(+) T cells expressed memory markers at high levels. However, among controls with lower mycobacterial antigen exposure in Boston, we found significantly lower frequencies of T cells staining with CD1b tetramers loaded with mycobacterial lipids. These data link CD1b-specific T cell detection to mycobacterial exposure, but not TB disease status, which potentially explains differences in outcomes among CD1-based clinical studies, which used control subjects with low Mtb exposure. Frontiers Media S.A. 2020-02-14 /pmc/articles/PMC7033476/ /pubmed/32117314 http://dx.doi.org/10.3389/fimmu.2020.00199 Text en Copyright © 2020 Lopez, Iwany, Suliman, Reijneveld, Ocampo, Jimenez, Calderon, Lecca, Murray, Moody and Van Rhijn. http://creativecommons.org/licenses/by/4.0/ 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) and the copyright owner(s) 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 Lopez, Kattya Iwany, Sarah K. Suliman, Sara Reijneveld, Josephine F. Ocampo, Tonatiuh A. Jimenez, Judith Calderon, Roger Lecca, Leonid Murray, Megan B. Moody, D. Branch Van Rhijn, Ildiko CD1b Tetramers Broadly Detect T Cells That Correlate With Mycobacterial Exposure but Not Tuberculosis Disease State |
title | CD1b Tetramers Broadly Detect T Cells That Correlate With Mycobacterial Exposure but Not Tuberculosis Disease State |
title_full | CD1b Tetramers Broadly Detect T Cells That Correlate With Mycobacterial Exposure but Not Tuberculosis Disease State |
title_fullStr | CD1b Tetramers Broadly Detect T Cells That Correlate With Mycobacterial Exposure but Not Tuberculosis Disease State |
title_full_unstemmed | CD1b Tetramers Broadly Detect T Cells That Correlate With Mycobacterial Exposure but Not Tuberculosis Disease State |
title_short | CD1b Tetramers Broadly Detect T Cells That Correlate With Mycobacterial Exposure but Not Tuberculosis Disease State |
title_sort | cd1b tetramers broadly detect t cells that correlate with mycobacterial exposure but not tuberculosis disease state |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7033476/ https://www.ncbi.nlm.nih.gov/pubmed/32117314 http://dx.doi.org/10.3389/fimmu.2020.00199 |
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