Affinity and kinetics of the interactions between an αβ T-cell receptor and its superantigen and class II-MHC/peptide ligands

1997 ◽  
Vol 34 (6) ◽  
pp. 493-503 ◽  
Author(s):  
Sanjay S. Khandekar ◽  
Pamela P. Brauer ◽  
Jerome W. Naylor ◽  
Hsiu-Ching Chang ◽  
Petra Kern ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Class Ii ◽  
Peptide Ligands ◽  
Class Ii Mhc ◽  
Kinetics Of

The Density of the Class II MHC T Cell Receptor Ligand Influences IFN-γ/IL-4 Ratios in Immune Responsesin Vivo

1998 ◽  
Vol 183 (1) ◽  
pp. 70-79 ◽  
Author(s):  
Lisa DiMolfetto ◽  
Heather A. Neal ◽  
Adrian Wu ◽  
Christina Reilly ◽  
David Lo
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Class Ii ◽  
Receptor Ligand ◽  
Class Ii Mhc ◽  
Ifn Γ

Binary and ternary complexes between T-cell receptor, class II MHC and superantigen in vitro

Nature ◽  
1994 ◽  
Vol 369 (6478) ◽  
pp. 324-327 ◽  
Author(s):  
Alpna Seth ◽  
Lawrence J. Stern ◽  
Tom H. M. Ottenhoff ◽  
Isaac Engel ◽  
Michael J. Owen ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Class Ii ◽  
Ternary Complexes ◽  
Binary And Ternary Complexes ◽  
Class Ii Mhc

scholarly journals P02.02 Generating neo- and self-antigen screening libraries for class II HLA presentation

2020 ◽  
Vol 8 (Suppl 2) ◽  
pp. A20.2-A20
Author(s):  
V Pinamonti ◽  
N Felix ◽  
JM Lindner
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Tumor Antigens ◽  
Cell Receptor ◽  
Class Ii ◽  
Patient Specific ◽  
Spectrometric Analysis ◽  
Cross Presentation ◽  
Class Ii Mhc ◽  
Antigen Presenting

BackgroundThe identification of neo-antigens presented by tumor cells is an essential tool for cancer prevention, diagnosis, and therapy. Current approaches frequently involve mass spectrometric analysis, but these workflows do not concomitantly identify the cognate T-cell receptor. Likewise, TCR functional screens are often limited to a subset of predicted neo-epitopes.Materials and MethodsHere, we present a new method for the generation of an un-biased antigen-presenting library. Due to the genomic instability of tumors, patient-specific libraries will be cloned using random primers, ensuring the cloning of tumor-specific transcribed regions. This approach will not only address class I presentation of intracellular tumor antigens, but is also designed to simultaneously screen for cross-presentation on class II MHC complexes by professional antigen-presenting cells, an increasingly important component of anti-tumor immune responses. To guarantee presentation of genetically encoded antigens on class II MHC complexes, a signal motif for chaperone-mediated autophagy (CMA) is introduced in front of the cDNA sequence. Furthermore, antigens will be processed by the intracellular machinery, avoiding potential restrictions on spliced peptides.ConclusionsOnce established, these libraries can be exploited in high-throughput screens to functionally identify neo-antigens together with their corresponding T-cell receptor.Disclosure InformationV. Pinamonti: Other; Significant; Janssen. N. Felix: Other; Significant; Janssen. J.M. Lindner: Other; Significant; Janssen.

Structure and specificity of a class II MHC alloreactive gamma delta T cell receptor heterodimer

Science ◽  
1989 ◽  
Vol 245 (4919) ◽  
pp. 746-749 ◽  
Author(s):  
L. Matis ◽  
A. Fry ◽  
R. Cron ◽  
M. Cotterman ◽  
R. Dick ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Class Ii ◽  
Gamma Delta ◽  
Class Ii Mhc ◽  
Gamma Delta T Cell

scholarly journals Positive and Negative Selection in Transgenic Mice Expressing a T-Cell Receptor Specific for Influenza Nucleoprotein and Endogenous Superantigen

1993 ◽  
Vol 3 (3) ◽  
pp. 159-174 ◽  
Author(s):  
Clio Mamalaki ◽  
James Elliott ◽  
Trisha Norton ◽  
Nicholas Yannoutsos ◽  
Alain R. Townsend ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Transgenic Mice ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Class Ii ◽  
Cytotoxic T Cell ◽  
Dependent Manner ◽  
Class Ii Mhc ◽  
Peripheral T Cells

A transgenic mouse was generated expressing on most (>80%) of thymocytes and peripheral T cells a T-cell receptor isolated from a cytotoxic T-cell clone (F5). This clone is CD8+and recognizes αα366-374 of the nucleoprotein (NP 366-374) of influenza virus (A/NT/60/68), in the context of Class ,MHC Db(Townsend et al., 1986). The receptor utilizes the Vβ11 and Vα4 gene segments for the β chain and α chain, respectively (Palmer et al., 1989). The usage of Vβ11 makes this TcR reactive to Class II IE molecules and an endogenous ligand recently identified as a product of the endogenous mammary tumour viruses (Mtv) 8, 9, and 11 (Dyson et al., 1991). Here we report the development of F5 transgenic T cells and their function in mice of the appropriate MHC (C57BL/10 H-2b, IE-) or in mice expressing Class II MHC IE (e.g., CBA/Ca H-2kand BALB/c H-2d) and the endogenous Mtv ligands. Positive selection of CD8+T cells expressing the Vβ11 is seen in C57BL/10 transgenic mice (H-2b). Peripheral T cells from these mice are capable of killing target cells in an antigen-dependent manner after a period ofin vitroculture with IL-2. In the presence of Class II MHC IE molecules and the endogenous Mtv ligand, most of the single-positive cells carrying the transgenic T-cell receptor are absent in the thymus. Unexpectedly, CD8+peripheral T-cells in these (H-2kor H-2d) F5 mice are predominantly Vβ11 positive and also have the capacity to kill targets in an antigen-dependent manner. This is true even following backcrossing of the F5 TcR transgene to H-2dscid/scid mice, in which functional rearrangement of endogenous TcR alpha- and beta-chain genes is impaired.

Probing Molecular Interactions within Class II MHC Aq/Glycopeptide/T-Cell Receptor Complexes Associated with Collagen-Induced Arthritis

2007 ◽  
Vol 50 (23) ◽  
pp. 5627-5643 ◽  
Author(s):  
Ida E. Andersson ◽  
Balik Dzhambazov ◽  
Rikard Holmdahl ◽  
Anna Linusson ◽  
Jan Kihlberg
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Molecular Interactions ◽  
Cell Receptor ◽  
Class Ii ◽  
Collagen Induced Arthritis ◽  
Receptor Complexes ◽  
Class Ii Mhc

scholarly journals CD8 coreceptor-mediated focusing can reorder the agonist hierarchy of peptide ligands recognized via the T cell receptor

2020 ◽  
Author(s):  
Mathew Clement ◽  
Lea Knezevic ◽  
Tamsin Dockree ◽  
James E. McLaren ◽  
Kristin Ladell ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Theoretical Models ◽  
Cell Receptor ◽  
Dissociation Rate ◽  
Peptide Ligands ◽  
Controlled System ◽  
Peptide Antigens ◽  
Histocompatibility Complex ◽  
The Relationship

ABSTRACTCD8+ T cells are inherently cross-reactive and recognize numerous peptide antigens in the context of a given major histocompatibility complex class I (MHCI) molecule via the clonotypically expressed T cell receptor (TCR). The lineally expressed coreceptor CD8 interacts coordinately with MHCI at a distinct and largely invariant site to slow the TCR/peptide-MHCI (pMHCI) dissociation rate and enhance antigen sensitivity. However, this biological effect is not necessarily uniform, and theoretical models suggest that antigen sensitivity can be modulated in a differential manner by CD8. We used an intrinsically controlled system to determine how the relationship between the TCR/pMHCI interaction and the pMHCI/CD8 interaction affects the functional sensitivity of antigen recognition. Our data show that modulation of the pMHCI/CD8 interaction can reorder the agonist hierarchy of peptide ligands across a spectrum of affinities for the TCR.SIGNIFICANCESufficient immune coverage of the peptide universe within a finite host requires highly degenerate T cell receptors (TCRs). However, this inherent need for antigen cross-recognition is associated with a high risk of autoimmunity, which can only be mitigated by a process of adaptable specificity. We describe a mechanism that resolves this conundrum by allowing individual clonotypes to focus on specific peptide ligands without alterations to the structure of the TCR.

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