BCG vaccination at birth shapes the TCR usage and functional gene expression profile of MR1T cells at 9 weeks of age
5 affiliations
- 1Division of Infectious Diseases, Department of Pediatrics, Oregon Health & Science University
- 2Oregon National Primate Research Center, OHSU
- 3DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research; South African Medical Research Council Centre for Tuberculosis Research; Division of Immunology, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University
- 4South African Tuberculosis Vaccine Initiative, Division of Immunology, Department of Pathology and Institute of Infectious Disease and Molecular Medicine, University of Cape Town
- 5Division of Pulmonary, Allergy and Critical Care Medicine, Oregon Health & Science University
Abstract
Tuberculosis (TB) is the leading infectious disease killer worldwide and children suffer disproportionately. The ongoing burden of disease, despite widespread vaccination with BCG, highlights the need for novel vaccines. MR1-restricted T (MR1T) cells recognize small molecules, including microbial-derived molecules, presented by the monomorphic MHC class 1-related molecule (MR1). They have both “innate” effector capacity, allowing them to quickly respond to pathogens including Mycobacterium tuberculosis (Mtb), while also having adaptive features (effector memory cell surface phenotype and selective TCR usage). Feasibility of an MR1T cell-based vaccination remains underexplored and critical to this is whether or not MR1T cells possess the capacity for immunological memory. To begin to address this question, peripheral blood mononuclear cells (PBMC) were collected at 9-weeks of age from healthy term-infants in South Africa, who had either received BCG vaccination at birth (n = 10) or who had BCG vaccination delayed (n = 10). MR1/5-OP-RU tetramer positive cells were sorted using flow cytometry and single-cell RNA and TCR-seq was performed. Ex-vivo MR1T cells from vaccinated infants demonstrated increased expression of type I interferon response genes consistent with a cytokine mediated response to BCG vaccination. Using the TCR clustering algorithm TCRdist3, TCRs predicted to recognize similar antigens were grouped together, revealing a cluster significantly enriched in BCG-vaccinated infants. This cluster exhibited elevated expression of pro-inflammatory and cytotoxic genes, consistent with gene expression patterns driven by a TCR-mediated antigen-selective response to BCG. This work provides the first step in addressing if MR1T cells demonstrate immunological memory, however, further work is needed to understand if these clonal expansions persist and possess the capacity for antigenic recall.
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BibTeX
@article{kain2026vaccination,
title = {{BCG vaccination at birth shapes the TCR usage and functional gene expression profile of MR1T cells at 9 weeks of age}},
author = {Dylan Kain and G. W. McElfresh and Gwendolyn M. Swarbrick and Katherine H. Rott and Gregory Boggy and Gerhard Walzl and Nelita Du Plessis and Willem Hanekom and Elisa Nemes and Muki Shey and Thomas J. Scriba and Benjamin N. Bimber and David M. Lewinsohn and Deborah A. Lewinsohn},
journal = {Scientific Reports},
year = {2026},
month = jul,
doi = {10.1038/s41598-026-62158-2},
url = {https://doi.org/10.1038/s41598-026-62158-2},
note = {CC BY},
}
RIS
TY - JOUR
TI - BCG vaccination at birth shapes the TCR usage and functional gene expression profile of MR1T cells at 9 weeks of age
AU - Dylan Kain
AU - G. W. McElfresh
AU - Gwendolyn M. Swarbrick
AU - Katherine H. Rott
AU - Gregory Boggy
AU - Gerhard Walzl
AU - Nelita Du Plessis
AU - Willem Hanekom
AU - Elisa Nemes
AU - Muki Shey
AU - Thomas J. Scriba
AU - Benjamin N. Bimber
AU - David M. Lewinsohn
AU - Deborah A. Lewinsohn
PY - 2026
DA - 2026/07/01
JO - Scientific Reports
DO - 10.1038/s41598-026-62158-2
UR - https://doi.org/10.1038/s41598-026-62158-2
AB - Tuberculosis (TB) is the leading infectious disease killer worldwide and children suffer disproportionately. The ongoing burden of disease, despite widespread vaccination with BCG, highlights the need for novel vaccines. MR1-restricted T (MR1T) cells recognize small molecules, including microbial-derived molecules, presented by the monomorphic MHC class 1-related molecule (MR1). They have both “innate” effector capacity, allowing them to quickly respond to pathogens including Mycobacterium tuberculosis (Mtb), while also having adaptive features (effector memory cell surface phenotype and selective TCR usage). Feasibility of an MR1T cell-based vaccination remains underexplored and critical to this is whether or not MR1T cells possess the capacity for immunological memory. To begin to address this question, peripheral blood mononuclear cells (PBMC) were collected at 9-weeks of age from healthy term-infants in South Africa, who had either received BCG vaccination at birth (n = 10) or who had BCG vaccination delayed (n = 10). MR1/5-OP-RU tetramer positive cells were sorted using flow cytometry and single-cell RNA and TCR-seq was performed. Ex-vivo MR1T cells from vaccinated infants demonstrated increased expression of type I interferon response genes consistent with a cytokine mediated response to BCG vaccination. Using the TCR clustering algorithm TCRdist3, TCRs predicted to recognize similar antigens were grouped together, revealing a cluster significantly enriched in BCG-vaccinated infants. This cluster exhibited elevated expression of pro-inflammatory and cytotoxic genes, consistent with gene expression patterns driven by a TCR-mediated antigen-selective response to BCG. This work provides the first step in addressing if MR1T cells demonstrate immunological memory, however, further work is needed to understand if these clonal expansions persist and possess the capacity for antigenic recall.
SN - 2045-2322
ER -