scholarly journals Structural determination of lipid antigens captured at the CD1d–T-cell receptor interface

2017 ◽  
Vol 114 (31) ◽  
pp. 8348-8353 ◽  
Author(s):  
Patrick J. Brennan ◽  
Tan-Yun Cheng ◽  
Daniel G. Pellicci ◽  
Gerald F. M. Watts ◽  
Natacha Veerapen ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Receptor ◽  
Sterile Inflammation ◽  
Inkt Cells ◽  
Lipid Antigens ◽  
Lipid Antigen ◽  
Specific Antigens ◽  
Fragmentation Patterns ◽  
Endogenous Lipids

Glycolipid antigens recognized by αβ T-cell receptors (TCRs) drive the activation of invariant natural killer T (iNKT) cells, a specialized subset of innate T lymphocytes. Glycolipids with α-linked anomeric carbohydrates have been identified as potent microbial lipid antigens for iNKT cells, and their unusual α-anomeric linkage has been thought to define a “foreign” lipid antigen motif. However, mammals use endogenous lipids to select iNKT cells, and there is compelling evidence for iNKT cell responses in various types of sterile inflammation. The nature of endogenous or environmental lipid antigens encountered by iNKT cells is not well defined. Here, we sought to identify lipid antigens in cow’s milk, a prominent part of the human diet. We developed a method to directly capture lipid antigens within CD1d–lipid–TCR complexes, while excluding CD1d bound to nonantigenic lipids, followed by direct biochemical analysis of the lipid antigens trapped at the TCR–CD1d interface. The specific antigens captured by this “TCR trap” method were identified as α-linked monohexosylceramides by mass spectrometry fragmentation patterns that distinguished α- from β-anomeric monohexosylceramides. These data provide direct biochemical evidence for α-linked lipid antigens from a common dietary source.

CD1d–lipid-antigen recognition by the semi-invariant NKT T-cell receptor

Nature ◽  
2007 ◽  
Vol 448 (7149) ◽  
pp. 44-49 ◽  
Author(s):  
Natalie A. Borg ◽  
Kwok S. Wun ◽  
Lars Kjer-Nielsen ◽  
Matthew C. J. Wilce ◽  
Daniel G. Pellicci ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Antigen Recognition ◽  
Lipid Antigen

scholarly journals Folliculotropic Mycosis Fungoides with Skewed T-cell Receptor CDR3 Motif: Suggestive of Lipid-antigen Selection?

2017 ◽  
Vol 97 (9) ◽  
pp. 1081-1086 ◽  
Author(s):  
P Mantaka ◽  
A Malecka ◽  
G Trøen ◽  
P Helsing ◽  
P Gjersvik ◽  
...  
Keyword(s):  
T Cell ◽  
Mycosis Fungoides ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Lipid Antigen ◽  
Antigen Selection

scholarly journals SOX4 controls invariant NKT cell differentiation by tuning TCR signaling

2018 ◽  
Vol 215 (11) ◽  
pp. 2887-2900 ◽  
Author(s):  
Nidhi Malhotra ◽  
Yilin Qi ◽  
Nicholas A. Spidale ◽  
Michela Frascoli ◽  
Bing Miu ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lineage ◽  
High Mobility ◽  
Allergic Diseases ◽  
Cell Receptor ◽  
Inkt Cells ◽  
Tcr Signaling ◽  
Nkt Cell ◽  
Essential Function ◽  
Lineage Diversification

Natural killer T (NKT) cells expressing the invariant T cell receptor (iTCR) serve an essential function in clearance of certain pathogens and have been implicated in autoimmune and allergic diseases. Complex effector programs of these iNKT cells are wired in the thymus, and upon thymic egress, they can respond within hours of antigenic challenges, classifying iNKT cells as innate-like. It has been assumed that the successful rearrangement of the invariant iTCRα chain is the central event in the divergence of immature thymocytes to the NKT cell lineage, but molecular properties that render the iTCR signaling distinct to permit the T cell lineage diversification remain obscure. Here we show that the High Mobility Group (HMG) transcription factor (TF) SOX4 controls the production of iNKT cells by inducing MicroRNA-181 (Mir181) to enhance TCR signaling and Ca2+ fluxes in precursors. These results suggest the existence of tailored, permissive gene circuits in iNKT precursors for innate-like T cell development.

scholarly journals Cytotoxic T lymphocytes specific for self tumor immunoglobulin express T cell receptor delta chain.

1989 ◽  
Vol 169 (5) ◽  
pp. 1557-1564 ◽  
Author(s):  
A Wright ◽  
J E Lee ◽  
M P Link ◽  
S D Smith ◽  
W Carroll ◽  
...  
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
B Cell ◽  
T Cell Receptor ◽  
Cytotoxic T Lymphocytes ◽  
Cell Receptor ◽  
Transformed Cells ◽  
Adoptive Therapy ◽  
Specific Antigens

CTL are thought to play a role in the elimination of transformed cells in vivo. The effectiveness of such CTL is in part dependent on recognition of tumor specific antigens. Among the best characterized tumor-specific antigens are the unique or idiotypic determinants on the Ig of B cell lymphomas. Here we describe the generation and properties of human CTL specific for the idiotype on autologous B cell tumors. These cells are CD3+,CD4-,CD8- and express the delta chain of the TCR. Such cells may prove useful in tumor-specific adoptive therapy.

scholarly journals Determination of Interaction Kinetics between the T Cell Receptor and Peptide-Loaded MHC Class II via Single-Molecule Diffusion Measurements

2012 ◽  
Vol 103 (2) ◽  
pp. L17-L19 ◽  
Author(s):  
Markus Axmann ◽  
Johannes B. Huppa ◽  
Mark M. Davis ◽  
Gerhard J. Schütz
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Mhc Class Ii ◽  
Single Molecule ◽  
Cell Receptor ◽  
Class Ii ◽  
Interaction Kinetics

scholarly journals The Total Synthesis of Proposed Immunoactive Glycolipids from S. Pneumoniae and a Re-evaluation of Their Immunological Activity

2021 ◽  
Author(s):  
Seyed Iraj Sadraei ◽  
Greg Yousif ◽  
S. Maryamdokht Taimoory ◽  
Emmanuel Igbokwe ◽  
Samaneh Mehri ◽  
...  
Keyword(s):  
T Cell ◽  
Total Synthesis ◽  
T Cell Receptor ◽  
Mammalian Species ◽  
White Blood Cells ◽  
Computational Modelling ◽  
Cell Receptor ◽  
Binary Complex ◽  
Inkt Cells ◽  
High Degree

<p>Invariant natural killer T cells (iNKT), a subclass of white blood cells, are responsible for the production of pro-inflammatory cytokines which induce a systemic immune response. They are distinctive in having an invariant T-cell receptor that recognizes glycolipid antigens presented by the class I major histocompatibility complex-related protein CD1d, which is conserved across multiple mammalian species in a class of proteins well-renowned for their high degree of polymorphism. This receptor’s first identified antigen is the potent KRN7000, a glycosphingolipid isolated from bacteria that were found on a Japanese marine sponge. The corresponding terrestrial antigen remained unidentified until quite recently, when diacylglycerol-containing glycolipids, reported to activate iNKT cells, were isolated from <i>Streptococcus pneumoniae</i>. We report the total synthesis and immunological re-evaluation of these two glycolipids. The compounds are unable to activate iNKT cells. Computational modelling shows that these ligands, while being capable of interacting with the CD1d receptor, create a different surface for the binary complex that makes formation of the ternary complex with the iNKT T-cell receptor difficult. Together these results suggest that the reported activity might have been due to an impurity in the original isolated sample, and highlights the importance of taking care when reporting biological activity from isolated natural products.<b></b></p>

scholarly journals High-throughput determination of the antigen specificities of T cell receptors in single cells

2018 ◽  
Author(s):  
Shu-Qi Zhang ◽  
Ke-Yue Ma ◽  
Alexandra A. Schonnesen ◽  
Mingliang Zhang ◽  
Chenfeng He ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
High Throughput ◽  
Single Cells ◽  
Cell Receptor ◽  
Cross Reactivity ◽  
Wild Type ◽  
Type Antigen

We present tetramer-associated T-cell receptor sequencing (TetTCR-Seq), a method to link T cell receptor (TCR) sequences to their cognate antigens in single cells at high throughput. Binding is determined using a library of DNA-barcoded antigen tetramers that is rapidly generated by in vitro transcription and translation. We applied TetTCR-Seq to identify patterns in TCR cross-reactivity with cancer neo-antigens and to rapidly isolate neo-antigen-specific TCRs with no cross-reactivity to the wild-type antigen.

scholarly journals Ovalbumin antigen-specific activation of T cell receptor closely resembles soluble antibody stimulation as revealed by BOOST phosphotyrosine proteomics

2021 ◽  
Author(s):  
Xien Yu Chua ◽  
Arthur Salomon
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tyrosine Phosphorylation ◽  
Cell Receptor ◽  
Binding Affinities ◽  
Spectrum Optimization ◽  
Wide Scale ◽  
Specific Antigens ◽  
Definition Of

Activation of T cell receptors (TCR) leads to a network of early signaling predominantly orchestrated by tyrosine phosphorylation in T cells. TCR are commonly activated using soluble anti-TCR antibodies, but this approach is not antigen-specific. Alternatively, activating the TCR using specific antigens of a range of binding affinities in the form of peptide-major histocompatibility complex (pMHC) is presumed to be more physiological. However, due to the lack of wide-scale phosphotyrosine (pTyr) proteomic studies directly comparing anti-TCR antibodies and pMHC, a comprehensive definition of these activated states remains enigmatic. Elucidation of the tyrosine phosphoproteome using quantitative pTyr proteomics enables a better understanding of the unique features of these activating agents and the role of ligand binding affinity on signaling. Here, we apply the recently established Broad-spectrum Optimization Of Selective Triggering (BOOST) to examine perturbations in tyrosine phosphorylation of TCR triggered by anti-TCR antibodies and pMHC. Our data reveals that high-affinity ovalbumin (OVA) pMHC activation of the TCR triggers a largely similar, albeit potentially stronger, pTyr-mediated signaling regulatory axis compared to anti-TCR antibody. Signaling output resulting from OVA pMHC variants correlates well with their weaker affinities, enabling affinity-tunable control of signaling strength. Collectively, we provide a framework for applying BOOST to compare pTyr-mediated signaling pathways of T cells activated in an antigen-independent and antigen-specific manner.

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