A polymorphism in human CD1A is associated with susceptibility to tuberculosis

Seshadri, Chetan; Thuong, Nt T. T.; Yen, N.T.; Bang, Nguyen Duc; Chau, Tran Thi Hong; Thwaites, Guy; Dunstan, Sarah J.; Hawn, Thomas R.

doi:10.1038/gene.2014.5

Cited by 30 publications

(29 citation statements)

References 14 publications

(15 reference statements)

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“…These data highlight the need to understand the distinct functions of CD1a, CD1b, and CD1c. Though CD1 proteins exhibit limited structural variation, a polymorphism in CD1a that is associated with low surface expression and T-cell activation was shown to be associated with TB [55], [56]. CD1b is expressed in TB granulomas and may locally activate lipid reactive T-cells [57].…”

Section: Mycobacterial Antigen Presentation By Cd1mentioning

confidence: 99%

Harnessing donor unrestricted T-cells for new vaccines against tuberculosis

Joosten

Ottenhoff

Lewinsohn

et al. 2019

Vaccine

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Mycobacterium bovis bacille Calmette-Guérin (BCG) prevents extrapulmonary tuberculosis (TB) and death among infants but fails to consistently and sufficiently prevent pulmonary TB in adults. Thus, TB remains the leading infectious cause of death worldwide, and new vaccine approaches are urgently needed. T-cells are important for protective immunity to Mycobacterium tuberculosis (Mtb), but the optimal T-cell antigens to be included in new vaccines are not established. T-cells are often thought of as responding mainly to peptide antigens presented by polymorphic major histocompatibility complex (MHC) I and II molecules. Over the past two decades, the number of non-peptidic Mtb derived antigens for αβ and γδ T-cells has expanded rapidly, creating broader perspectives about the types of molecules that could be targeted by T-cell-based vaccines against TB. Many of these non-peptide responsive T-cell subsets in humans are activated in a manner that is unrestricted by classical MHC-dependent antigen-presenting systems, but instead require essentially nonpolymorphic presentation systems. These systems are Cluster of differentiation 1 (CD1), MHC related protein 1 (MR1), butyrophilin 3A1, as well as the nonclassical MHC class Ib family member HLA-E. Thus, the resulting T-cell responses can be shared among a genetically diverse population, creating the concept of donor-unrestricted T-cells (DURTs). Here, we review evidence that DURTs are an abundant component of the human immune system and recognize many antigens expressed by Mtb, including antigens that are expressed in BCG and other candidate whole cell vaccines. Further, DURTs exhibit functional diversity and demonstrate the ability to control microbial infection in small animal models. Finally, we outline specific knowledge gaps and research priorities that must be addressed to realize the full potential of DURTs as part of new TB vaccines approaches.

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Section: Mycobacterial Antigen Presentation By Cd1mentioning

confidence: 99%

Harnessing donor unrestricted T-cells for new vaccines against tuberculosis

Joosten

Ottenhoff

Lewinsohn

et al. 2019

Vaccine

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“…Group 1 CD1 T cell responses correlate with mycobacterial load such that patients with active tuberculosis had higher frequencies of mycolic acid specific T cells (producing IL-2 and/or IFN-γ) than those subjects who had been treated for tuberculosis, although with substantial despite variability among patients (54). Although they have limited genetic variation, polymorphisms in CD1a are associated with susceptibility to M. tuberculosis infection (55). Nonetheless, the conserved conformation of the CD1 proteins makes CD1-restricted T cells an attractive target for vaccines and lipid based vaccination trials have shown partial protection in a highly susceptible animal model (56).…”

Section: Conventional Cd8 T Cells Unconventional Cd8 T Cells and Unimentioning

confidence: 99%

CD8 T cells and Mycobacterium tuberculosis infection

2015

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Tuberculosis is primarily a respiratory disease that is caused by Mycobacterium tuberculosis. M. tuberculosis can persist and replicate in macrophages in vivo, usually in organized cellular structures called granulomas. There is substantial evidence for the importance of CD4 T cells in control of tuberculosis, but the evidence for a requirement for CD8 T cells in this infection has not been proven in humans. However, animal model data support a non-redundant role for CD8 T cells in control of M. tuberculosis infection, and in humans, infection with this pathogen leads to generation of specific CD8 T cell responses. These responses include classical (MHC Class I restricted) and non-classical CD8 T cells. Here, we discuss the potential roles of CD8 T cells in defense against tuberculosis, and our current understanding of the wide range of CD8 T cell types seen in M. tuberculosis infection.

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“…It is difficult to imagine that human populations have such sequence variation, but humans and chimpanzees share the same sequence in the α1 and α2 domains of the MR1 protein. In regard to CD1 genes, SNPs in the α1 domain (104, 105) and the non-coding regions (106) of the human CD1a and CD1d genes have been identified, and non-synonymous mutations have also been deduced from exon 2 of both genes (107). Few identified SNPs support that MR1 and CD1 genes are still very conserved and appear similar to innate immune receptors such as TLRs in terms of sequence stability in human populations.…”

Section: Highly Conserved Antigen-presenting Moleculesmentioning

confidence: 99%

Targeting Innate-Like T Cells in Tuberculosis

Huang

2016

Front. Immunol.

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Peptide-specific conventional T cells have been major targets for designing most antimycobacterial vaccines. Immune responses mediated by conventional T cells exhibit a delayed onset upon primary infection and are highly variable in different human populations. In contrast, innate-like T cells quickly respond to pathogens and display effector functions without undergoing extensive clonal expansion. Specifically, the activation of innate-like T cells depends on the promiscuous interaction of highly conserved antigen-presenting molecules, non-peptidic antigens, and likely semi-invariant T cell receptors. In antimicrobial immune responses, mucosal-associated invariant T cells are activated by riboflavin precursor metabolites presented by major histocompatibility complex-related protein I, while lipid-specific T cells including natural killer T cells are activated by lipid metabolites presented by CD1 proteins. Multiple innate-like T cell subsets have been shown to be protective or responsive in mycobacterial infections. Through rapid cytokine secretion, innate-like T cells function in early defense and memory response, offering novel advantages over conventional T cells in the design of anti-tuberculosis strategies.

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A polymorphism in human CD1A is associated with susceptibility to tuberculosis

Cited by 30 publications

References 14 publications

Harnessing donor unrestricted T-cells for new vaccines against tuberculosis

Harnessing donor unrestricted T-cells for new vaccines against tuberculosis

CD8 T cells and Mycobacterium tuberculosis infection

Targeting Innate-Like T Cells in Tuberculosis

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