The Conventional Nature of Non-MHC-Restricted T Cells

Lepore, Marco; Mori, Lucia; Libero, Gennaro De

doi:10.3389/fimmu.2018.01365

Cited by 29 publications

(34 citation statements)

References 122 publications

(176 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An attractive alternative approach is to exploit non-polymorphic HLA molecules such as HLA-E, HLA-G, CD1 and MR1 [86,87]. CD1 and MR1, in particular, have recently attracted interest in this space, following the identification of T cell clones able to recognise CD1-or MR1presented antigens expressed by tumour cells [88]. Interestingly, CD1 and MR1 present lipids and metabolites, respectively, which show distinct chemistry, cellular biosynthetic and catabolic pathways, in vivo distribution and abundance from peptides.…”

Section: Overcoming Hla Restrictionmentioning

confidence: 99%

Novel TCR-based biologics: mobilising T cells to warm ‘cold’ tumours

Lowe

Cole

Kenefeck

et al. 2019

Cancer Treatment Reviews

Self Cite

View full text Add to dashboard Cite

Immunotherapeutic strategies have revolutionised cancer therapy in recent years, bringing meaningful improvements in outcomes for patients with previously intractable conditions. These successes have, however, been largely limited to certain types of liquid tumours and a small subset of solid tumours that are known to be particularly immunogenic. Broadening these advances across the majority of tumour indications, which are characterised by an immune-excluded, immune-deserted or immune-suppressed ('cold') phenotype, will require alternative approaches that are able to specifically address this unique biological environment. Several newer therapeutic modalities, including adoptive cell therapy and T cell redirecting bispecific molecules, are considered to hold particular promise and are being investigated in early phase clinical trials across various solid tumour indications. ImmTAC molecules are a novel class of T cell redirecting bispecific biologics that exploit TCR-based targeting of tumour cells; providing potent and highly specific access to the vast landscape of intracellular targets. The first of these reagents to reach the clinic, tebentafusp (IMCgp100), has generated demonstrable clinical efficacy in an immunologically cold solid tumour with a high unmet need. Here, we highlight the key elements of the ImmTAC platform that make it ideally positioned to overcome the cold tumour microenvironment in an off-the-shelf format.

show abstract

Section: Overcoming Hla Restrictionmentioning

confidence: 99%

Novel TCR-based biologics: mobilising T cells to warm ‘cold’ tumours

Lowe

Cole

Kenefeck

et al. 2019

Cancer Treatment Reviews

Self Cite

View full text Add to dashboard Cite

show abstract

“…On the other hand, lipids, glycolipids, and lipopeptides, are presented to T cells by the non-polymorphic CD1 molecules ( 9 ). Several Mtb lipid antigens are presented by CD1 molecules such as CD1a, CD1b, CD1c, and CD1d, increasing the breadth of the T-cell responses to Mtb ( 10 – 12 ).…”

Section: Introductionmentioning

confidence: 99%

“…A variety of Mtb lipid antigens are presented to T cells in association with CD1b ( 10 – 12 ). One mycobacterial antigen, in particular, belonging to the group of diacylated sulfoglycolipids and identified as 2-palmitoyl or 2-stearoyl-3-hydroxyphthioceranoyl-2′-sulfate-α-α’-d-trehalose (Ac 2 SGL), was found to be expressed by virulent Mtb bacilli and presented by CD1b ( 13 ).…”

Section: Introductionmentioning

confidence: 99%

A Direct Role for the CD1b Endogenous Spacer in the Recognition of a Mycobacterium tuberculosis Antigen by T-Cell Receptors

et al. 2020

View full text Add to dashboard Cite

Lipids, glycolipids and lipopeptides derived from Mycobacterium tuberculosis (Mtb) are presented to T cells by monomorphic molecules known as CD1. This is the case of the Mtb-specific sulfoglycolipid Ac 2 SGL, which is presented by CD1b molecules and is recognized by T cells found in tuberculosis (TB) patients and in individuals with latent infections. Our group, using filamentous phage display technology, obtained two specific ligands against the CD1b-Ac 2 SGL complex: (i) a single chain T cell receptor (scTCR) from a human T cell clone recognizing the CD1b-AcSGL complex; and (ii) a light chain domain antibody (dAbκ11). Both ligands showed lower reactivity to a synthetic analog of Ac 2 SGL (SGL12), having a shorter acyl chain as compared to the natural antigen. Here we put forward the hypothesis that the CD1b endogenous spacer lipid (EnSpacer) plays an important role in the recognition of the CD1b-Ac 2 SGL complex by specific T cells. To support this hypothesis we combined: (a) molecular binding assays for both the scTCR and the dAbκ11 antibody domain against a small panel of synthetic Ac 2 SGL analogs having different acyl chains, (b) molecular modeling of the CD1b-Ac 2 SGL/EnSpacer complex, and (c) modeling of the interactions of this complex with the scTCR. Our results contribute to understand the mechanisms of lipid presentation by CD1b molecules and their interactions with T-cell receptors and other specific ligands, which may help to develop specific tools targeting Mtb infected cells for therapeutic and diagnostic applications.

show abstract

“…Addition of an implant in the context of tissue damage may modulate the natural adaptive damage response by modifying self-antigens or impacting antigen presentation. Finally, there is evidence that T cells can specifically respond to non-peptidic repeating structures such as sugars and lipids and thus may recognize repeating polymer structures [61,62]. Regardless of the antigen or combination of antigens, the type 17 immune response is activated and directing key aspects of the FBR and targeting this pathway has therapeutic benefits for biocompatibility.…”

Section: Canonical Activation Of T Cells Requires Presentation Of Antmentioning

confidence: 99%

Interleukin-17 and senescence regulate the foreign body response

Chung

Maestas

Lebid

et al. 2019

Preprint

View full text Add to dashboard Cite

AbstractSynthetic biomaterials and medical devices suffer to varying levels from fibrosis via the foreign body response (FBR). To explore mechanistic connections between the immune response and fibrosis from the FBR, we first analyzed fibrotic capsule surrounding human breast implants and found increased numbers of interleukin (IL)17-producing γδ+T cells and CD4+TH17 cells as well as senescent cells. Further analysis in a murine model demonstrated an early innate IL17 response to synthetic implants, mediated by innate lymphoid cells and γδ+T cells, was followed by a chronic adaptive antigen dependent CD4+TH17 cell response. Mice deficient in IL17 signaling established that IL17 was required for the fibrotic response to materials and the development of p16INK4asenescent cells. Treatment with a senolytic agent reduced IL17 expression and fibrosis. Discovery of a feed-forward loop between the TH17 and senescence response to synthetic materials introduces new targets for therapeutic intervention in the foreign body response.

show abstract

The Conventional Nature of Non-MHC-Restricted T Cells

Cited by 29 publications

References 122 publications

Novel TCR-based biologics: mobilising T cells to warm ‘cold’ tumours

Novel TCR-based biologics: mobilising T cells to warm ‘cold’ tumours

A Direct Role for the CD1b Endogenous Spacer in the Recognition of a Mycobacterium tuberculosis Antigen by T-Cell Receptors

Interleukin-17 and senescence regulate the foreign body response

Contact Info

Product

Resources

About