Human γδ T cells recognize CD1b by two distinct mechanisms

Reijneveld, Josephine F.; Ocampo, Tonatiuh A.; Shahine, Adam; Gully, Benjamin S.; Vantourout, Pierre; Hayday, Adrian; Rossjohn, Jamie; Moody, D. Branch; Rhijn, Ildiko Van

doi:10.1073/pnas.2010545117

Cited by 46 publications

(33 citation statements)

References 53 publications

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“…This supports the notion that Vδ1 may have a particular predilection for CD1c 33 , as it does for CD1d 52, 53, 54, 55 . Along with the recent discovery of CD1b-reactive Vδ1 + γδ T cells 65 , it now appears that at least 3 members of the CD1 family can be recognised by Vδ1 + T cells. These observations add to a growing number of TCR genes that are similarly enriched in multiple CD1-restricted T cell populations 50 , suggesting a possible co-evolution between CD1 molecules and certain TCR genes.…”

Section: Discussionmentioning

confidence: 99%

CD36 family members are TCR-independent ligands for CD1 antigen-presenting molecules

Gherardin

Redmond

McWilliam

et al. 2021

Preprint

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CD1c presents lipid-based antigens to CD1c-restricted T cells which are thought to be a major component of the human T cell pool. The study of CD1c-restricted T cells, however, is hampered by the presence of an abundantly expressed CD1c-binding partner on blood cells distinct to the T cell receptor (TCR), confounding analysis of TCR-mediated CD1c tetramer staining. Here, we identify the CD36 family (CD36, CD36-L1 and CD36-L2) as novel ligands for CD1c, CD1b and CD1d proteins, and show that CD36 is the receptor responsible for non-TCR-mediated CD1c tetramer staining of blood cells. Moreover, CD36-blockade enables tetramer-based identification of CD1c-restricted T cells and clarifies identification of CD1b- and CD1d-restricted T cells. We use this technique to characterise CD1c-restricted T cells ex vivo and show diverse phenotypic features, TCR repertoire and antigen-specific subsets. Accordingly, this work will enable further studies into the biology of CD1 and human CD1-restricted T cells.

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Section: Discussionmentioning

confidence: 99%

CD36 family members are TCR-independent ligands for CD1 antigen-presenting molecules

Gherardin

Redmond

McWilliam

et al. 2021

Preprint

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“…It is important to note that the Vδ1 subtype represents a large proportion of these reactive cells ( 143 ), therefore it is suspected that Vδ1 cells can contribute to antitumor immunity through a CD1-dependent pathway. Recently, it was discovered that these cells with Vδ1 TCR, specifically Vγ4Vδ1 cells, detected CD1b in transfected LCs while they producing IFN-γ after recognition ( 146 ). These cells also recognized BTN-like (BTNL) proteins, such as BTNL3 and BTNL8, which suggests that CD1b-reactive γδ T cells may respond through the engagement and bispecific combination of CD1b and BTNLs ( 13 ).…”

Section: γδ T Cells and Leukemia: The Leukemic Microenvironment Mattersmentioning

confidence: 99%

γδ T Cells for Leukemia Immunotherapy: New and Expanding Trends

et al. 2021

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Recently, many discoveries have elucidated the cellular and molecular diversity in the leukemic microenvironment and improved our knowledge regarding their complex nature. This has allowed the development of new therapeutic strategies against leukemia. Advances in biotechnology and the current understanding of T cell-engineering have led to new approaches in this fight, thus improving cell-mediated immune response against cancer. However, most of the investigations focus only on conventional cytotoxic cells, while ignoring the potential of unconventional T cells that until now have been little studied. γδ T cells are a unique lymphocyte subpopulation that has an extensive repertoire of tumor sensing and may have new immunotherapeutic applications in a wide range of tumors. The ability to respond regardless of human leukocyte antigen (HLA) expression, the secretion of antitumor mediators and high functional plasticity are hallmarks of γδ T cells, and are ones that make them a promising alternative in the field of cell therapy. Despite this situation, in particular cases, the leukemic microenvironment can adopt strategies to circumvent the antitumor response of these lymphocytes, causing their exhaustion or polarization to a tumor-promoting phenotype. Intervening in this crosstalk can improve their capabilities and clinical applications and can make them key components in new therapeutic antileukemic approaches. In this review, we highlight several characteristics of γδ T cells and their interactions in leukemia. Furthermore, we explore strategies for maximizing their antitumor functions, aiming to illustrate the findings destined for a better mobilization of γδ T cells against the tumor. Finally, we outline our perspectives on their therapeutic applicability and indicate outstanding issues for future basic and clinical leukemia research, in the hope of contributing to the advancement of studies on γδ T cells in cancer immunotherapy.

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“…The T-cell interactome is notably diverse, and both α/β and γ/δ T-cells have been linked with self-recognition mediated by varied types of antigen presenting molecules. Self-recognition of antigen presenting molecules has been reported for CD1a 6,25 , CD1b 20,26 , CD1c 20 , CD1d 14,22,27 , or MR1 7 , thus providing evidence for the rather complex molecular network associated to T-cells.…”

Section: Discussionmentioning

confidence: 98%

“…The T-cell interactome is notably diverse, and both a/b and g/d T-cells have been linked with self-recognition mediated by varied types of antigen presenting molecules. Self-recognition of antigen presenting molecules has been reported for CD1a 6,25 , CD1b 20,26 , CD1c 20 , CD1d 14,22,27 , or MR1 7 , thus providing evidence for the rather complex molecular network associated to T-cells. Because the class and relative abundance of the bound lipids could play a role in the recruitment of EPCR-T-cells, we mapped the lipid profile of EPCR and revealed PS, PI and SM species in low quantities.…”

Section: Discussionmentioning

confidence: 99%

A novel α/β T-cell subpopulation defined by recognition of EPCR

Erausquin

Morán-Garrido

Sáiz

et al. 2021

Preprint

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T-cell self-recognition of antigen presenting molecules is led by antigen-dependent or independent mechanisms. The endothelial protein C receptor (EPCR) shares remarkable similarity with CD1d, including a lipid binding cavity. We identified EPCR-specific α/β T-cells in human peripheral blood of healthy donors. The average frequency in the CD3+ leukocyte pool is comparable to other autoreactive T-cell subsets that specifically bind MHC-like receptors. Alteration of the EPCR lipid cargo, revealed by X-ray diffraction studies, points to a prevalent, yet not exclusive, lipid-independent self-recognition. In addition, we solve the EPCR lipidome, and detect species not yet described as EPCR ligands. These studies report, for the first time, novel recognition by circulating α/β T-cells and provide grounds for EPCR and lipid mediated T-cell restriction.

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Human γδ T cells recognize CD1b by two distinct mechanisms

Cited by 46 publications

References 53 publications

CD36 family members are TCR-independent ligands for CD1 antigen-presenting molecules

CD36 family members are TCR-independent ligands for CD1 antigen-presenting molecules

γδ T Cells for Leukemia Immunotherapy: New and Expanding Trends

A novel α/β T-cell subpopulation defined by recognition of EPCR

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