Detailed characterization of human <i>Mycobacterium tuberculosis</i> specific HLA‐E restricted CD8<sup>+</sup> T cells

Prezzemolo, Teresa; Meijgaarden, Krista E. van; Franken, Kees L. M. C.; Caccamo, Nadia; Dieli, Francesco; Ottenhoff, Tom H. M.; Joosten, Simone A.

doi:10.1002/eji.201747184

Cited by 42 publications

(47 citation statements)

References 37 publications

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“…Twenty-seven HLA-E alleles have been reported to date, but most are found infrequently or as non-functional proteins [7][8][9]. HLA-E exists predominantly in the human population as two alleles, HLA-E*0101 and HLA-E*0103, varying by an arginine or a glycine at amino acid position 107, respectively [10,11].…”

Section: Vaccines For Emerging Pathogens: From Research To the Clinicmentioning

confidence: 99%

“…These non-canonical T cells contribute to the majority of T cells present during active Mtb infection [77], and overshadow T cells restricted by canonical HLA class Ia epitope presentation [78,79]. Mtb antigens presented by HLA-E to CD8 + T cells can induce either a cytotoxic or regulatory phenotype, consequently inhibiting Mtb pathogenesis and growth in infected macrophages [7,78]. HLA-E : Mtb-restricted T cells from active TB infection express a type 2 cytokine profile with increased interleukin (IL)-4 and IL-10 production, and assist B cells with antibody and cytokine production to inhibit Mtb growth [65,76,77].…”

Section: Mycobacterium Tuberculosismentioning

confidence: 99%

“…PART 1 Twenty-seven HLA-E alleles have been reported to date, but most are found infrequently or as non-functional proteins [7][8][9]. PART 1 Twenty-seven HLA-E alleles have been reported to date, but most are found infrequently or as non-functional proteins [7][8][9].…”

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confidence: 99%

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HLA-E: exploiting pathogen-host interactions for vaccine development

Sharpe

Bowyer

Brackenridge

et al. 2019

Clinical and Experimental Immunology

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Summary Viruses, when used as vectors for vaccine antigen delivery, can induce strong cellular and humoral responses against target epitopes. Recent work by Hansen et al. describes the use of a cytomegalovirus‐vectored vaccine, which is able to generate a stable effector‐memory T cell population at the sites of vaccination in rhesus macaques. This vaccine, targeted towards multiple epitopes in simian immunodeficiency virus (SIV), did not induce classical CD8+ T cells. However, non‐canonical CD8+ T cell induction occurred via major histocompatibility complex (MHC) class II and MHC‐E. The MHC‐E‐restricted T cells could recognize broad epitopes across the SIV peptides, and conferred protection against viral challenge to 55% of vaccinated macaques. The human homologue, human leucocyte antigen (HLA)‐E, is now being targeted as a new avenue for vaccine development. In humans, HLA‐E is an unusually oligomorphic class Ib MHC molecule, in comparison to highly polymorphic MHC class Ia. Whereas MHC class Ia presents peptides derived from pathogens to T cells, HLA‐E classically binds defined leader peptides from class Ia MHC peptides and down‐regulates NK cell cytolytic activity when presented on the cell surface. HLA‐E can also restrict non‐canonical CD8+ T cells during natural infection with various pathogens, although the extent to which they are involved in pathogen control is mostly unknown. In this review, an overview is provided of HLA‐E and its ability to interact with NK cells and non‐canonical T cells. Also discussed are the unforeseen beneficial effects of vaccination, including trained immunity of NK cells from bacille Calmette–Guérin (BCG) vaccination, and the broad restriction of non‐canonical CD8+ T cells by cytomegalovirus (CMV)‐vectored vaccines in pre‐clinical trials.

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Section: Vaccines For Emerging Pathogens: From Research To the Clinicmentioning

confidence: 99%

Section: Mycobacterium Tuberculosismentioning

confidence: 99%

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HLA-E: exploiting pathogen-host interactions for vaccine development

Sharpe

Bowyer

Brackenridge

et al. 2019

Clinical and Experimental Immunology

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“…Studies of DURTS suggest that they contribute to protective immunity, with MR1 restriction involved in responses against Mycobacterium bovis via BCG vaccination 83 , and Klebsiella pneumoniae 84,85 , and both CD1 86 and HLA-E 87,88 mediated responses contributing to Mtb control. It is not yet clear, however, if these are memory responses that can be generated through vaccination.…”

Section: E a Systematic Antigen Discovery Approach In Humansmentioning

confidence: 99%

Research and development of new tuberculosis vaccines: a review

2018

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Tuberculosis kills more people worldwide than any other single infectious disease agent, a threat made more dire by the spread of drug-resistant strains of Mycobacterium tuberculosis (Mtb). Development of new vaccines capable of preventing TB disease and new Mtb infection are an essential component of the strategy to combat the TB epidemic. Accordingly, the WHO considers the development of new TB vaccines a major public health priority. In October 2017, the WHO convened a consultation with global leaders in the TB vaccine development field to emphasize the WHO commitment to this effort and to facilitate creative approaches to the discovery and development of TB vaccine candidates. This review summarizes the presentations at this consultation, updated with scientific literature references, and includes discussions of the public health need for a TB vaccine; the status of efforts to develop vaccines to replace or potentiate BCG in infants and develop new TB vaccines for adolescents and adults; strategies being employed to diversify vaccine platforms; and new animal models being developed to facilitate TB vaccine development. A perspective on the status of these efforts from the major funders and organizational contributors also is included. This presentation highlights the extraordinary progress being made to develop new TB vaccines and provided a clear picture of the exciting development pathways that are being explored.

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“…Alternatively it can also present sequences from intracellular pathogens including Mtb [32,[69][70][71]. Detailed characterization of these cells revealed a unique Th2 cytokine repertoire [72][73][74]. Compared to individuals with latent TB, patients with active TB disease had higher frequencies of Mtb-specific HLA-E restricted cells that decreased over time during treatment [72][73][74].…”

Section: Protection Mediated By Unconventional T-cell Subsetsmentioning

confidence: 99%

Friends and foes of tuberculosis: modulation of protective immunity

Brighenti

Joosten

2018

J Intern Med

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Protective immunity in tuberculosis (TB) is subject of debate in the TB research community, as this is key to fully understand TB pathogenesis and to develop new promising tools for TB diagnosis and prognosis as well as a more efficient TB vaccine. IFN-γ producing CD4 T cells are key in TB control, but may not be sufficient to provide protection. Additional subsets have been identified that contribute to protection such as multifunctional and cytolytic T-cell subsets, including classical and nonclassical T cells as well as novel innate immune cell subsets resulting from trained immunity. However, to define protective immune responses against TB, the complexity of balancing TB immunity also has to be considered. In this review, insights into effector cell immunity and how this is modulated by regulatory cells, associated comorbidities and the host microbiome, is discussed. We systematically map how different suppressive immune cell subsets may affect effector cell responses at the local site of infection. We also dissect how common comorbidities such as HIV, helminths and diabetes may bias protective TB immunity towards pathogenic and regulatory responses. Finally, also the composition and diversity of the microbiome in the lung and gut could affect host TB immunity. Understanding these various aspects of the immunological balance in the human host is fundamental to prevent TB infection and disease.

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Detailed characterization of human Mycobacterium tuberculosis specific HLA‐E restricted CD8⁺ T cells

Cited by 42 publications

References 37 publications

HLA-E: exploiting pathogen-host interactions for vaccine development

HLA-E: exploiting pathogen-host interactions for vaccine development

Research and development of new tuberculosis vaccines: a review

Friends and foes of tuberculosis: modulation of protective immunity

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Detailed characterization of human Mycobacterium tuberculosis specific HLA‐E restricted CD8+ T cells

Cited by 42 publications

References 37 publications

HLA-E: exploiting pathogen-host interactions for vaccine development

HLA-E: exploiting pathogen-host interactions for vaccine development

Research and development of new tuberculosis vaccines: a review

Friends and foes of tuberculosis: modulation of protective immunity

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Detailed characterization of human Mycobacterium tuberculosis specific HLA‐E restricted CD8⁺ T cells