Narcissistic T cells: reactivity to self makes a difference

Paprčková, Darina; Štěpánek, Ondřej

doi:10.1111/febs.15498

Cited by 7 publications

(9 citation statements)

References 84 publications

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“…The purpose of the present paper, as with its predecessors, 4,7,8 has been to document the growing recognition of positive repertoire selection and its role in alloresponsiveness, and to suggest its mechanistic basis 2 . Results with mice 17 are being increasing confirmed for humans 9,18 and emphasize the role in generating the diversity of T cell subsets of the ‘variable signal strengths’ obtained during ‘early encounters with subthreshold ligands in the thymus’ 19 . An absence of T cell receptor cross‐linking at low thymic ligand concentrations may be necessary for positive selection, 20 in keeping with a second inhibitory signal at higher concentrations, as discussed elsewhere 7,21 …”

Section: Why the Delay?mentioning

confidence: 99%

Positive selection of immune repertoires: A short further history

Forsdyke

2022

Scand J Immunol

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The importance of the negative selection of self‐reacting cells from immune repertoires was easily recognized since it would militate against autoimmune disease. However, while the existence of positive selection in the auditioning of newly formed immune cells is now recognized, it is taking longer to understand its role. With the removal or suppression by negative selection of a subset of immune cells that self‐react, would the specificities of remaining immune cells range widely to confront the universe of ‘non‐self’ antigens, including some borne by potential microbial pathogens? Alternatively, from among those remaining immune cells, could some be picked out (positively selected) based on ‘advanced knowledge’ of some character likely to be common to those pathogens? To exploit ‘holes’ created by negative selection, it was predicted that pathogens would attempt to mimic their hosts by progressive stepwise mutation towards host ‘self’—a process entailing passage through a host anti‐‘near‐self‐reactivity’ arena. Anticipating this, those hosts that over evolutionary time ‘learned’ to positively select from developing immune repertoires, cells with reactivities against ‘near‐self’, would be advantaged by natural selection. The benefits of this narrowing of the range of host immune reactivities are now clearer and may solve Burnet's paradox, which concerns the ability of an organism's immune cells to attack its own cancer cells. However, while supporting this in the context of T cell immunity, Manczinger and his colleagues now suggest that some wily pathogens may be exploiting their hosts' narrow defence foci by ‘seeking’, through mutation, dissimilarity from host ‘self’.

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Section: Why the Delay?mentioning

confidence: 99%

Positive selection of immune repertoires: A short further history

Forsdyke

2022

Scand J Immunol

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“…Generation and analysis of mouse TCR expressing Jurkat T cells 1×10 6 of Jurkat T cells with TCR OTI-b and human CD8ab (40) were transduced with TCRa genes in MSCV-ires-GFP vectors as described previously (40). Briefly, Jurkat cells were resuspended in MSCV pseudovirus-containing supernatant supplemented with 8 mg/mL of polybrene and centrifuged (45 min, 1200 g, 30°C).…”

Section: Cell Counting and Cell Culturementioning

confidence: 99%

“…It has been established that strongly self-reactive clones differentiate into regulatory T cells or unconventional T-cell subsets in the thymus [reviewed in (5)]. Recently, it has been documented that the relative level of self-reactivity contributes to steady-state T-cell heterogeneity as well as to inter-clonal differences within the T-cell immune response in the periphery [reviewed in (6)]. In helper CD4 + T cells, the relative level of selfreactivity determines the primary and memory T-cell responses (7) and their differentiation into Th1 vs. Tfh effector subsets (8).…”

Section: Introductionmentioning

confidence: 99%

Self-reactivity of CD8 T-cell clones determines their differentiation status rather than their responsiveness in infections

Paprčková

Niederlová²,

Moudrá³

et al. 2022

Front. Immunol.

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Mature T cells are selected for recognizing self-antigens with low to intermediate affinity in the thymus. Recently, the relative differences in self-reactivity among individual T-cell clones were appreciated as important factors regulating their fate and immune response, but the role of self-reactivity in T-cell biology is incompletely understood. We addressed the role of self-reactivity in T-cell diversity by generating an atlas of mouse peripheral CD8+ T cells, which revealed two unconventional populations of antigen-inexperienced T cells. In the next step, we examined the steady-state phenotype of monoclonal T cells with various levels of self-reactivity. Highly self-reactive clones preferentially differentiate into antigen-inexperienced memory-like cells, but do not form a population expressing type I interferon-induced genes, showing that these two subsets have unrelated origins. The functional comparison of naïve monoclonal CD8+ T cells specific to the identical model antigen did not show any correlation between the level of self-reactivity and the magnitude of the immune response.

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“…Circulating naive T cells continuously survey their local environments with their TCRs via interactions with self-pMHCs which generates survival signals, so called tonic signaling (5)(6)(7)(8)(9)(10). Those naive T cells that fail to engage self-pMHCs rapidly die (11,12).…”

Section: T Cells Need To Properly Discriminate Among Foreign Self- mentioning

confidence: 99%

Adapting T Cell Receptor Ligand Discrimination Capability via LAT

Weiss

2021

Front. Immunol.

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Self- and non-self ligand discrimination is a core principle underlying T cell-mediated immunity. Mature αβ T cells can respond to a foreign peptide ligand presented by major histocompatibility complex molecules (pMHCs) on antigen presenting cells, on a background of continuously sensed self–pMHCs. How αβ T cells can properly balance high sensitivity and high specificity to foreign pMHCs, while surrounded by a sea of self-peptide ligands is not well understood. Such discrimination cannot be explained solely by the affinity parameters of T cell antigen receptor (TCR) and pMHC interaction. In this review, we will discuss how T cell ligand discrimination may be molecularly defined by events downstream of the TCR–pMHC interaction. We will discuss new evidence in support of the kinetic proofreading model of TCR ligand discrimination, and in particular how the kinetics of specific phosphorylation sites within the adaptor protein linker for activation of T cells (LAT) determine the outcome of TCR signaling. In addition, we will discuss emerging data regarding how some kinases, including ZAP-70 and LCK, may possess scaffolding functions to more efficiently direct their kinase activities.

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Narcissistic T cells: reactivity to self makes a difference

Cited by 7 publications

References 84 publications

Positive selection of immune repertoires: A short further history

Positive selection of immune repertoires: A short further history

Self-reactivity of CD8 T-cell clones determines their differentiation status rather than their responsiveness in infections

Adapting T Cell Receptor Ligand Discrimination Capability via LAT

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