
==== Front
bioRxiv
BIORXIV
bioRxiv
2692-8205
Cold Spring Harbor Laboratory

10.1101/2024.08.26.609630
preprint
1
Article
Mtb specific HLA-E restricted T cells are induced during Mtb infection but not after BCG administration in non-human primates and humans
Voogd Linda http://orcid.org/0000-0002-0523-8929

van Wolfswinkel Marjolein
Satti Iman
White Andrew D.
Dijkman Karin
Gela Anele
van Meijgaarden Krista E.
Franken Kees L.M.C.
Marshall Julia L.
Ottenhoff Tom H.M.
Scriba Thomas J. http://orcid.org/0000-0002-0641-1359

McShane Helen
Sharpe Sally A.
Verreck Frank A.W.
Joosten Simone A.
26 8 2024
2024.08.26.609630https://creativecommons.org/licenses/by-nd/4.0/ This work is licensed under a Creative Commons Attribution-NoDerivatives 4.0 International License, which allows reusers to copy and distribute the material in any medium or format in unadapted form only, and only so long as attribution is given to the creator. The license allows for commercial use.
http://biorxiv.org/lookup/doi/10.1101/2024.08.26.609630
nihpp-2024.08.26.609630.pdf
Abstract

Novel vaccines targeting the world’s deadliest pathogen Mycobacterium tuberculosis ( Mtb ) are urgently needed as the efficacy of the Bacillus Calmette–Guérin (BCG) vaccine in its current use is limited. HLA-E is a virtually monomorphic unconventional antigen presentation molecule and HLA-E restricted Mtb specific CD8 + T cells can control intracellular Mtb growth, making HLA-E a promising vaccine target for Mtb . In this study, we evaluated the frequency and phenotype of HLA-E restricted Mtb specific CD4 + /CD8 + T cells in the circulation and bronchoalveolar lavage fluid of two independent non-human primate (NHP) studies and from humans receiving BCG either intradermally or mucosally. BCG vaccination followed by Mtb challenge in NHPs did not affect the frequency of circulating and local HLA-E/ Mtb CD4 + and CD8 + T cells, and we saw the same in humans receiving BCG. HLA-E/ Mtb T cell frequencies were significantly increased after Mtb challenge in unvaccinated NHPs, which was correlated with higher TB pathology. Together, HLA-E/ Mtb restricted T cells are minimally induced by BCG in humans and rhesus macaques (RMs) but can be elicited after Mtb infection in unvaccinated RMs. These results give new insights into targeting HLA-E as a potential immune mechanism against TB.
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