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  1. Article ; Online: Aging unconventionally: γδ T cells, iNKT cells, and MAIT cells in aging.

    Kurioka, Ayako / Klenerman, Paul

    Seminars in immunology

    2023  Volume 69, Page(s) 101816

    Abstract: Unconventional T cells include γδ T cells, invariant Natural Killer T cells (iNKT) cells and Mucosal Associated Invariant T (MAIT) cells, which are distinguished from conventional T cells by their recognition of non-peptide ligands presented by non- ... ...

    Abstract Unconventional T cells include γδ T cells, invariant Natural Killer T cells (iNKT) cells and Mucosal Associated Invariant T (MAIT) cells, which are distinguished from conventional T cells by their recognition of non-peptide ligands presented by non-polymorphic antigen presenting molecules and rapid effector functions that are pre-programmed during their development. Here we review current knowledge of the effect of age on unconventional T cells, from early life to old age, in both mice and humans. We then discuss the role of unconventional T cells in age-associated diseases and infections, highlighting the similarities between members of the unconventional T cell family in the context of aging.
    MeSH term(s) Humans ; Mice ; Animals ; Mucosal-Associated Invariant T Cells ; Natural Killer T-Cells ; Aging
    Language English
    Publishing date 2023-08-01
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 1018141-6
    ISSN 1096-3618 ; 1044-5323
    ISSN (online) 1096-3618
    ISSN 1044-5323
    DOI 10.1016/j.smim.2023.101816
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  2. Article ; Online: MAITs and their mates: "Innate-like" behaviors in conventional and unconventional T cells.

    Hackstein, Carl-Philipp / Klenerman, Paul

    Clinical and experimental immunology

    2023  Volume 213, Issue 1, Page(s) 1–9

    Abstract: Most CD4 and CD8 T cells are restricted by conventional major histocompatibility complex (MHC) molecules and mount TCR-dependent adaptive immune responses. In contrast, MAIT, iNKT, and certain γδ TCR bearing cells are characterized by their abilities to ... ...

    Abstract Most CD4 and CD8 T cells are restricted by conventional major histocompatibility complex (MHC) molecules and mount TCR-dependent adaptive immune responses. In contrast, MAIT, iNKT, and certain γδ TCR bearing cells are characterized by their abilities to recognize antigens presented by unconventional antigen-presenting molecules and to mount cytokine-mediated TCR-independent responses in an "innate-like" manner. In addition, several more diverse T-cell subsets have been described that in a similar manner are restricted by unconventional antigen-presenting molecules but mainly depend on their TCRs for activation. Vice versa, innate-like behaviour was reported in defined subpopulations of conventional T cells, particularly in barrier sites, showing that these two features are not necessarily linked. The abilities to recognize antigens presented by unconventional antigen-presenting molecules or to mount TCR-independent responses creates unique niches for these T cells and is linked to wide range of functional capabilities. This is especially exemplified by unconventional and innate-like T cells present at barrier sites where they are involved in pathogen defense, tissue homeostasis as well as in pathologic processes.
    MeSH term(s) T-Lymphocyte Subsets ; Receptors, Antigen, T-Cell ; Antigens ; Cytokines
    Chemical Substances Receptors, Antigen, T-Cell ; Antigens ; Cytokines
    Language English
    Publishing date 2023-05-12
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 218531-3
    ISSN 1365-2249 ; 0009-9104 ; 0964-2536
    ISSN (online) 1365-2249
    ISSN 0009-9104 ; 0964-2536
    DOI 10.1093/cei/uxad058
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  3. Article ; Online: The (gradual) rise of memory inflation.

    Klenerman, Paul

    Immunological reviews

    2018  Volume 283, Issue 1, Page(s) 99–112

    Abstract: Memory inflation, as a term, has been used for 15 years now to describe the longitudinal development of stable, expanded ... ...

    Abstract Memory inflation, as a term, has been used for 15 years now to describe the longitudinal development of stable, expanded CD8
    MeSH term(s) Animals ; Antigen Presentation ; Antigen-Presenting Cells/immunology ; Antigen-Presenting Cells/metabolism ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/metabolism ; Humans ; Immunity, Cellular ; Immunologic Memory ; Models, Biological ; Phenotype
    Language English
    Publishing date 2018-04-17
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 391796-4
    ISSN 1600-065X ; 0105-2896
    ISSN (online) 1600-065X
    ISSN 0105-2896
    DOI 10.1111/imr.12653
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  4. Article ; Online: Adenovirus vector and mRNA vaccines: Mechanisms regulating their immunogenicity.

    Provine, Nicholas M / Klenerman, Paul

    European journal of immunology

    2022  Volume 53, Issue 6, Page(s) e2250022

    Abstract: Replication-incompetent adenovirus (Ad) vector and mRNA-lipid nanoparticle (LNP) constructs represent two modular vaccine platforms that have attracted substantial interest over the past two decades. Due to the COVID-19 pandemic and the rapid development ...

    Abstract Replication-incompetent adenovirus (Ad) vector and mRNA-lipid nanoparticle (LNP) constructs represent two modular vaccine platforms that have attracted substantial interest over the past two decades. Due to the COVID-19 pandemic and the rapid development of multiple successful vaccines based on these technologies, there is now clear real-world evidence of the utility and efficacy of these platforms. Considerable optimization and refinement efforts underpin the successful application of these technologies. Despite this, our understanding of the specific pathways and processes engaged by these vaccines to stimulate the immune response remains incomplete. This review will synthesize our current knowledge of the specific mechanisms by which CD8
    MeSH term(s) Humans ; mRNA Vaccines ; Pandemics ; COVID-19/prevention & control ; Genetic Vectors/genetics ; Adenoviridae/genetics
    Chemical Substances mRNA Vaccines
    Language English
    Publishing date 2022-11-20
    Publishing country Germany
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 120108-6
    ISSN 1521-4141 ; 0014-2980
    ISSN (online) 1521-4141
    ISSN 0014-2980
    DOI 10.1002/eji.202250022
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  5. Article ; Online: MR1: An unconventional twist in the tail.

    Phalora, Prabhjeet / Klenerman, Paul

    The Journal of cell biology

    2022  Volume 221, Issue 12

    Abstract: MR1 is a conserved molecule that binds microbial vitamin B metabolites and presents them to unconventional T cells. Lim and colleagues (2022. J. Cell Biol.https://doi.org/10.1083/jcb.202110125) uncover the role of AP2 in ensuring MR1 surface presentation, ...

    Abstract MR1 is a conserved molecule that binds microbial vitamin B metabolites and presents them to unconventional T cells. Lim and colleagues (2022. J. Cell Biol.https://doi.org/10.1083/jcb.202110125) uncover the role of AP2 in ensuring MR1 surface presentation, which relies on an atypical motif within the MR1 cytoplasmic tail.
    MeSH term(s) Antigen Presentation ; Histocompatibility Antigens Class I/metabolism ; Minor Histocompatibility Antigens/metabolism ; T-Lymphocytes ; Humans ; Vitamin B Complex/metabolism ; Adaptor Protein Complex 2/metabolism
    Chemical Substances Histocompatibility Antigens Class I ; Minor Histocompatibility Antigens ; MR1 protein, human ; Vitamin B Complex (12001-76-2) ; Adaptor Protein Complex 2
    Language English
    Publishing date 2022-11-14
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 218154-x
    ISSN 1540-8140 ; 0021-9525
    ISSN (online) 1540-8140
    ISSN 0021-9525
    DOI 10.1083/jcb.202211016
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  6. Article ; Online: Emerging features of MAIT cells and other unconventional T cell populations in human viral disease and vaccination.

    Hackstein, Carl-Philipp / Klenerman, Paul

    Seminars in immunology

    2022  Volume 61-64, Page(s) 101661

    Abstract: MAIT cells are one representative of a group of related unconventional or pre-set T cells, and are particularly abundant in humans. While these unconventional T cell types, which also include populations of Vδ2 cells and iNKT cells, recognise quite ... ...

    Abstract MAIT cells are one representative of a group of related unconventional or pre-set T cells, and are particularly abundant in humans. While these unconventional T cell types, which also include populations of Vδ2 cells and iNKT cells, recognise quite distinct ligands, they share functional features including the ability to sense "danger" by integration of cytokine signals. Since such signals are common to many human pathologies, activation of MAIT cells in particular has been widely observed. In this review we will discuss recent trends in these data, for example the findings from patients with Covid-19 and responses to novel vaccines. Covid-19 is an example where MAIT cell activation has been correlated with disease severity by several groups, and the pathways leading to activation are being clarified, but the overall role of the cells in vivo requires further exploration. Given the potential wide functional responsiveness of these cells, which ranges from tissue repair to cytotoxicity, and likely impacts on the activity of many other cell populations, defining the role of these cells - not only as sensitive biomarkers but also as mediators - across human disease remains an important task.
    MeSH term(s) Humans ; Mucosal-Associated Invariant T Cells/metabolism ; COVID-19 ; Cytokines/metabolism ; Lymphocyte Activation
    Chemical Substances Cytokines
    Language English
    Publishing date 2022-10-28
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1018141-6
    ISSN 1096-3618 ; 1044-5323
    ISSN (online) 1096-3618
    ISSN 1044-5323
    DOI 10.1016/j.smim.2022.101661
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  7. Article ; Online: Protection against SARS-CoV-2 after Vaccination and Previous Infection. Reply.

    Hopkins, Susan / Hall, Victoria / Klenerman, Paul

    The New England journal of medicine

    2022  Volume 386, Issue 26, Page(s) 2535

    MeSH term(s) COVID-19/prevention & control ; COVID-19 Vaccines ; Humans ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus ; Vaccination
    Chemical Substances COVID-19 Vaccines ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
    Language English
    Publishing date 2022-06-15
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 207154-x
    ISSN 1533-4406 ; 0028-4793
    ISSN (online) 1533-4406
    ISSN 0028-4793
    DOI 10.1056/NEJMc2205618
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  8. Article ; Online: Exposed seronegative: Cellular immune responses to SARS-CoV-2 in the absence of seroconversion.

    Jay, Cecilia / Ratcliff, Jeremy / Turtle, Lance / Goulder, Philip / Klenerman, Paul

    Frontiers in immunology

    2023  Volume 14, Page(s) 1092910

    Abstract: The factors determining whether infection will occur following exposure to SARS-CoV-2 remain elusive. Certain SARS-CoV-2-exposed individuals mount a specific T-cell response but fail to seroconvert, representing a population that may provide further ... ...

    Abstract The factors determining whether infection will occur following exposure to SARS-CoV-2 remain elusive. Certain SARS-CoV-2-exposed individuals mount a specific T-cell response but fail to seroconvert, representing a population that may provide further clarity on the nature of infection susceptibility and correlates of protection against SARS-CoV-2. Exposed seronegative individuals have been reported in patients exposed to the blood-borne pathogens Human Immunodeficiency virus and Hepatitis C virus and the sexually transmitted viruses Hepatitis B virus and Herpes Simplex virus. By comparing the quality of seronegative T-cell responses to SARS-CoV-2 with seronegative cellular immunity to these highly divergent viruses, common patterns emerge that offer insights on the role of cellular immunity against infection. For both SARS-CoV-2 and Hepatitis C, T-cell responses in exposed seronegatives are consistently higher than in unexposed individuals, but lower than in infected, seropositive patients. Durability of T-cell responses to Hepatitis C is dependent upon repeated exposure to antigen - single exposures do not generate long-lived memory T-cells. Finally, exposure to SARS-CoV-2 induces varying degrees of immune activation, suggesting that exposed seronegative individuals represent points on a spectrum rather than a discrete group. Together, these findings paint a complex landscape of the nature of infection but provide clues as to what may be protective early on in SARS-CoV-2 disease course. Further research on this phenomenon, particularly through cohort studies, is warranted.
    MeSH term(s) Humans ; SARS-CoV-2 ; Seroconversion ; COVID-19 ; Immunity, Cellular ; Hepacivirus ; Hepatitis C
    Language English
    Publishing date 2023-01-26
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2023.1092910
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  9. Article ; Online: Swimming Against the Current: MAIT Cell Function Is Preserved in the Peritoneum of Advanced Liver Disease Patients.

    Hackstein, Carl-Philipp / Klenerman, Paul

    Cellular and molecular gastroenterology and hepatology

    2020  Volume 9, Issue 4, Page(s) 709–710

    MeSH term(s) Humans ; Inflammation ; Liver Diseases ; Mucosal-Associated Invariant T Cells ; Peritoneal Cavity ; Peritoneum ; Peritonitis ; Swimming
    Language English
    Publishing date 2020-02-28
    Publishing country United States
    Document type Editorial ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Comment
    ISSN 2352-345X
    ISSN (online) 2352-345X
    DOI 10.1016/j.jcmgh.2020.02.002
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  10. Article ; Online: Indirect effects of cytomegalovirus infection: Implications for vaccine development.

    Moseley, Philip / Klenerman, Paul / Kadambari, Seilesh

    Reviews in medical virology

    2022  Volume 33, Issue 1, Page(s) e2405

    Abstract: Development of a cytomegalovirus (CMV) vaccine is a high priority due to its significant global impact-contributing to mortality in immunosuppressed individuals, neurodevelopmental delay in infected neonates and non-genetic sensorineural hearing loss. ... ...

    Abstract Development of a cytomegalovirus (CMV) vaccine is a high priority due to its significant global impact-contributing to mortality in immunosuppressed individuals, neurodevelopmental delay in infected neonates and non-genetic sensorineural hearing loss. The impact of CMV on the general population has been less well studied; however, a wide range of evidence indicates that CMV may increase the risk of atherosclerosis, cancer, immunosenescence, and progression of tuberculosis (TB) and human immunodeficiency virus. Due to the high seroprevalence of CMV worldwide, any modulation of risk by CMV is likely to have a significant impact on the epidemiology of these diseases. This review will evaluate how CMV may cause morbidity and mortality outside of the neonatal and immunosuppressed populations and consider the potential impact of a CMV vaccine on these outcomes.
    MeSH term(s) Infant, Newborn ; Humans ; Seroepidemiologic Studies ; Cytomegalovirus Infections/epidemiology ; Cytomegalovirus Infections/prevention & control ; Cytomegalovirus Vaccines ; Vaccine Development
    Chemical Substances Cytomegalovirus Vaccines
    Language English
    Publishing date 2022-11-15
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1086043-5
    ISSN 1099-1654 ; 1052-9276
    ISSN (online) 1099-1654
    ISSN 1052-9276
    DOI 10.1002/rmv.2405
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