Building conventions for unconventional lymphocytes

Pasman, Lesley; Kasper, Dennis L.

doi:10.1111/imr.12576

Cited by 18 publications

(15 citation statements)

References 79 publications

(184 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The most common antigens recognized by conventional T cells are peptide metabolites while the unconventional T cells respond to another group of very specific ligands (for recent reviews see refs. [1,2]) ( Fig. 1).…”

mentioning

confidence: 97%

MAIT cells as attractive vaccine targets

2019

View full text Add to dashboard Cite

Mucosal‐associated invariant T (MAIT) cells are a subset of T cells that perform innate‐like immunity functions upon recognition of small molecule vitamin B metabolites presented by the MHC, class I‐related protein‐1 (MR1). MAIT cells are profuse in humans, but especially abundant in blood, liver, lungs, and mucosal layers. The mucosa is a common site of carcinogenesis and MAIT cells have been found in both primary and metastatic tumors. MAIT cells target a host of microbes including Mycobacterium tuberculosis, Staphylococcus aureus, Salmonella enterica, Legionella longbeachae, Escherichia coli, and Candida albicans, and are highly activated in viral infections. Cytokines produced by MAIT cells are both anticancerous and antibacterial, but also have proinflammatory and possibly tumorigenic properties. In addition, it is believed that MAIT cells play a protective role in viral infections in an MR1‐independent fashion. Based on our summary of recent advances concerning both MR1‐mediated and MR1‐independent MAIT cell immune responses, we weigh the strengths and weaknesses of these cells for vaccine development.

show abstract

mentioning

confidence: 97%

MAIT cells as attractive vaccine targets

2019

View full text Add to dashboard Cite

show abstract

“…Surprisingly, only a 40-50% reduction in SFC frequency was seen when CD4 T cells were cultured with Mtb-infected MHCII −/− macrophages (Fig.3c). One possibility is that these CD4 T cells were nonconventional T cells 16, 17 ; another possibility is that these T cells were conventional T cells, but in the absence of MHC, their IFN-γ production was driven by IL-12 produced by the infected macrophages 18, 19 . When CD4 T cells were cocultured with Mtb-infected WT macrophages in the presence of blocking antibodies to IL-12, no reduction in T cell activation was observed (Fig.3d).…”

Section: Resultsmentioning

confidence: 99%

Limited recognition ofMycobacterium tuberculosis-infected macrophages by polyclonal CD4 and CD8 T cells from the lungs of infected mice

Patankar

Sutiwisesak

Boyce

et al. 2019

Preprint

View full text Add to dashboard Cite

20Immune responses following Mycobacterium tuberculosis (Mtb) infection or vaccination 21 are frequently assessed by measuring T cell recognition of crude Mtb antigens, 22 recombinant proteins, or peptide epitopes. We previously showed that not all Mtb-23 specific T cells recognize Mtb-infected macrophages. Thus, an important question is 24 what proportion of T cells elicited by Mtb infection recognize Mtb-infected macrophages. 25We answer this question by developing a modified elispot assay using viable Mtb-26 infected macrophages, a low multiplicity of infection and purified T cells. In C57BL/6 27 mice, CD4 and CD8 T cells were classically MHC restricted. Comparable frequencies of 28 T cells that recognize Mtb-infected macrophages were determined using interferon-γ 29 elispot and intracellular cytokine staining, and lung CD4 T cells more sensitively 30 recognized Mtb-infected macrophages than lung CD8 T cells. Compared to the numbers 31 of Mtb antigen-specific T cells for antigens such as ESAT-6 and TB10.4, low frequencies 32 of pulmonary CD4 and CD8 T cells elicited by aerosolized Mtb infection recognize Mtb-33 infected macrophages. Finally, we demonstrate that BCG vaccination elicits T cells that 34 recognize Mtb-infected macrophages. We propose that the frequency of T cells that 35 recognize infected macrophages could correlate with protective immunity and may be an 36 alternative approach to measuring T cell responses to Mtb antigens. 37with the failure of T cells specific for those antigens to recognize Mtb-infected 64 macrophages 4 . Importantly, following aerosol infection, Mtb disseminates to the 65 mediastinal lymph node, where T cells are first primed by dendritic cells, which then 66 expand and traffic to the lung 9, 10 . We speculate that there may be a mismatch in the 67 antigens presented (or cross-presented) by uninfected DC in the lymph nodes and 68 antigens presented by infected macrophages in the lung. Thus, T cells primed in the lymph 69 nodes during natural infection may not necessarily recognize antigens presented by Mtb-70 infected macrophages in the lung 11 . Regardless of the mechanism, we wondered whether 71 the inability of some T cells to recognize Mtb-infected macrophages might explain why the 72 number of antigen-specific T cells may not necessarily correlate with vaccine-induced 73 protection. 74To assess T cell recognition of Mtb-infected macrophages we developed a 75 modified elispot assay based on interferon (IFN)-g spot forming cells (SFC). Using a low 76 multiplicity of infection (MOI), we quantify the frequency of T cells that recognize Mtb-77 infected macrophages during primary infection in mice. We find that an unexpectedly low 78 frequency of ex vivo CD8 and CD4 T cells recognizes Mtb-infected macrophages. We 79 demonstrate that majority of the T cells from C57BL/6 mice that recognize Mtb-infected 80 macrophages are conventionally MHC-restricted T cells. Our data shows that CD4 T 81 cells efficiently detect Mtb-infected macrophages at a lower MOI, whereas CD8 T cells 82 on...

show abstract

“…What is clear however, is some of these MHCIb proteins present small molecules both exogenous and endogenous in origin recognized directly by the invariant TCRs of unconventional lymphocytes, and sizeable pools of the invariant clones capable of responding to their antigens are present and stable as a means of immune surveillance. The unconventional lymphocytes display a diverse array of antigen-driven effector functions, even within the same population, with some producing cytokines and helping B cells similar to CD4 T helper cells, while others acquire cytotoxic capacities like the CD8 and NK cells (8). Clearly, the unconventional lymphocytes play critical roles in bridging the gap between innate and adaptive immunity, but with so many of the MHCIb ligands unaccounted for, and with some ignorant to positive selection in the thymus, how many more populations of unconventional lymphocytes might be out there?…”

Section: Introductionmentioning

confidence: 99%

“…The unconventional lymphocytes display a diverse array of antigen-driven effector functions, even within the same population, with some producing cytokines and helping B cells similar to CD4 T helper cells, while others acquire cytotoxic capacities like the CD8 and NK cells. 8 Clearly, the unconventional lymphocytes play critical roles in bridging the gap between innate and adaptive immunity, but with so many of the MHCIb ligands unaccounted for, and with some ignorant to positive selection in the thymus, how many more populations of unconventional lymphocytes might be out there? Further complicating matters is that one of the unconventional T cell types (CD8αα + , double-negative IELs) we will discuss here are selected by both classical and non-classical MHCs and, after selection via highaffinity interactions with self-peptides, differentiates into a specialized, tolerogenic population.…”

Section: Introductionmentioning

confidence: 99%

Bohemian T cell receptors: sketching the repertoires of unconventional lymphocytes

Schattgen

Thomas

2018

Immunological Reviews

View full text Add to dashboard Cite

Over the last several decades, novel populations of unconventional T cells have been identified; defined by an invariant (or nearly invariant) T cell receptor (TCR) with a fixed specificity to non-canonical antigens and major histocompatibility (MHC) molecules, they form large, functionally monoclonal populations tasked with surveying for their specific antigens. With residence in both lymphoid and non-lymphoid tissues coupled with their ability to rapidly produce a spectrum of cytokines and effector molecules, the unconventional T cells are poised as some of the first responders to infection/damage and are thought to provide critical coverage before more focused, conventional T cell responses are mobilized. However, new technologies for the measurement and characterization of TCR repertoires have identified an underappreciated amount of TCR diversity in the unconventional T cells. In many cases, the specificities of these diverse TCRs converge on the same or similar antigens as their invariant counterparts, while others have yet to be defined. Here, we will review the current knowledge of the TCR repertoires of unconventional T cells and discuss how repertoires might be used as a framework for their organization, and further our understanding of their role not only during an immune response, but also their contribution in maintaining homeostasis.

show abstract

Building conventions for unconventional lymphocytes

Cited by 18 publications

References 79 publications

MAIT cells as attractive vaccine targets

MAIT cells as attractive vaccine targets

Limited recognition ofMycobacterium tuberculosis-infected macrophages by polyclonal CD4 and CD8 T cells from the lungs of infected mice

Bohemian T cell receptors: sketching the repertoires of unconventional lymphocytes

Contact Info

Product

Resources

About