scholarly journals Recognition of multiple peptide cores by a single T cell receptor.

1995 ◽  
Vol 182 (2) ◽  
pp. 531-539 ◽  
Author(s):  
N K Nanda ◽  
K K Arzoo ◽  
H M Geysen ◽  
A Sette ◽  
E E Sercarz
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Clone ◽  
Cell Receptor ◽  
Peptide Ligands ◽  
Present Evidence ◽  
Mhc Molecules ◽  
Histocompatibility Complex ◽  
T Cell Clone ◽  
Contact Residues

We present evidence that a single T cell clone can recognize at least five different overlapping peptides, each with its distinct core structure, in the context of the same major histocompatibility complex (MHC) molecule. Distinct core residues are crucial for triggering the T cell receptor (TCR) in each case. These results suggest that the TCR (a) has multiple sets of contact residues for alternative peptide-MHC ligands, the binding to any one of which can trigger the cell; and/or (b) is able to attach to the peptide-MHC complex in more than one orientation. In this sense, the TCR is a multisubsite structure capable of being stimulated by a variety of peptide ligands associated with the same MHC molecules.

scholarly journals Structural basis for T cell recognition of altered peptide ligands: a single T cell receptor can productively recognize a large continuum of related ligands.

1996 ◽  
Vol 184 (4) ◽  
pp. 1259-1268 ◽  
Author(s):  
G J Kersh ◽  
P M Allen
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Clone ◽  
Cell Receptor ◽  
Peptide Ligands ◽  
Structural Basis ◽  
Side Chain ◽  
Contact Residue ◽  
Altered Peptide Ligands ◽  
T Cell Clone

T cells recognize short linear peptides bound to major histocompatibility complex (MHC)-encoded molecules. Subtle molecular changes in peptide antigens produce altered peptide ligands (APLs), which induce different T cell responses from those induced by the antigenic ligand. A molecular basis for how these slight molecular variations lead to such different consequences for the T cell has not been described. To address this issue, we have made amino acid substitutions at the primary T cell receptor (TCR) contact residue of the murine hemoglobin determinant, Hb(64-76)/I-Ek and produced 12 peptides that interact with the TCR of the T cell clone 3.L2. The 3.L2 T cell responds to these peptides, which vary 1 million-fold in their activity, and enables them to be ranked according to their relative ability to signal through the 3.L2 TCR. Such a ranking reveals that the ability of the 3.L2 T cell to respond to these peptides depends on how well the structure of the side chain at the primary TCR contact site mimics that of the Asn residue present in the antigenic ligand. The reactivity of the 3.L2 T cell also depends on an MHC contact residue that is next to the primary TCR contact residue, suggesting that conformation of the Asn side chain is also important. By using nonnatural amino acids at a TCR contact residue, we have demonstrated that APLs can be rationally designed based on structure. These data are consistent with a model in which the affinity of a peptide-MHC complex for the TCR determines how the T cell will respond.

Specificity and T cell receptor β chain usage of a human collagen type II-reactive T cell clone derived from a healthy individual

1992 ◽  
Vol 22 (1) ◽  
pp. 51-56 ◽  
Author(s):  
Tan Yan ◽  
Harald Burkhardt ◽  
Thomas Ritter ◽  
Barbara Bröker ◽  
Karl Heinz Mann ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Collagen Type ◽  
Cell Clone ◽  
Cell Receptor ◽  
Type Ii ◽  
Collagen Type Ii ◽  
T Cell Clone ◽  
Human Collagen ◽  
Β Chain

scholarly journals Functional characterization of a T-cell receptor BV6+T-cell clone derived from a leprosy lesion

Immunology ◽  
2007 ◽  
Vol 120 (3) ◽  
pp. 354-361 ◽  
Author(s):  
Shereen Sabet ◽  
Maria-Teresa Ochoa ◽  
Peter A. Sieling ◽  
Thomas H. Rea ◽  
Robert L. Modlin
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Clone ◽  
Functional Characterization ◽  
Cell Receptor ◽  
T Cell Clone

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.

scholarly journals An invariant V alpha 24-J alpha Q/V beta 11 T cell receptor is expressed in all individuals by clonally expanded CD4-8- T cells.

1994 ◽  
Vol 180 (3) ◽  
pp. 1171-1176 ◽  
Author(s):  
P Dellabona ◽  
E Padovan ◽  
G Casorati ◽  
M Brockhaus ◽  
A Lanzavecchia
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Clone ◽  
Cell Subset ◽  
Cell Receptor ◽  
T Cell Subsets ◽  
T Cell Clone ◽  
Gene Usage ◽  
Beta Gene

The T cell receptor (TCR)-alpha/beta CD4-8- (double negative, DN) T cell subset is characterized by an oligoclonal repertoire and a restricted V gene usage. By immunizing mice with a DN T cell clone we generated two monoclonal antibodies (mAbs) against V alpha 24 and V beta 11, which have been reported to be preferentially expressed in DN T cells. Using these antibodies, we could investigate the expression and pairing of these V alpha and V beta gene products among different T cell subsets. V alpha 24 is rarely expressed among CD4+ and especially CD8+ T cells. In these cases it is rearranged to different J alpha segments, carries N nucleotides, and pairs with different V beta. Remarkably, V alpha 24 is frequently expressed among DN T cells and is always present as an invariant rearrangement with J alpha Q, without N region diversity. This invariant V alpha 24 chain is always paired to V beta 11. This unique V alpha 24-J alpha Q/V beta 11 TCR was found in expanded DN clones from all the individuals tested. These findings suggest that the frequent occurrence of cells carrying this invariant TCR is due to peripheral expansion of rare clones after recognition of a nonpolymorphic ligand.

Pathologic clonal cytotoxic T-cell responses: nonrandom nature of the T-cell–receptor restriction in large granular lymphocyte leukemia

Blood ◽  
2005 ◽  
Vol 106 (8) ◽  
pp. 2769-2780 ◽  
Author(s):  
Marcin W. Wlodarski ◽  
Christine O'Keefe ◽  
Evan C. Howe ◽  
Antonio M. Risitano ◽  
Alexander Rodriguez ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Clone ◽  
Clonal Selection ◽  
Cell Receptor ◽  
Large Granular Lymphocyte ◽  
Molecular Signature ◽  
Autoimmune Response ◽  
Cytotoxic T Cell ◽  
T Cell Clone

AbstractT-cell large granular lymphocyte (T-LGL) leukemia is a clonal lymphoproliferation of cytotoxic T cells (CTLs) associated with cytopenias. T-LGL proliferation seems to be triggered/sustained by antigenic drive; it is likely that hematopoietic progenitors are the targets in this process. The antigen-specific portion of the T-cell receptor (TCR), the variable beta (VB)–chain complementarity-determining region 3 (CDR3), can serve as a molecular signature (clonotype) of a T-cell clone. We hypothesized that clonal CTL proliferation develops not randomly but in the context of an autoimmune response. We identified the clonotypic sequence of T-LGL clones in 60 patients, including 56 with known T-LGL and 4 with unspecified neutropenia. Our method also allowed for the measurement of clonal frequencies; a decrease in or loss of the pathogenic clonotype and restoration of the TCR repertoire was found after hematologic remission. We identified 2 patients with identical immunodominant CDR3 sequence. Moreover, we found similarity between multiple immunodominant clonotypes and codominant as well as a nonexpanded, “supporting” clonotypes. The data suggest a nonrandom clonal selection in T-LGL, possibly driven by a common antigen. In contrast, the physiologic clonal CTL repertoire is highly diverse and we were not able to detect any significant clonal sharing in 26 healthy controls.

scholarly journals Immunization with soluble BDC 2.5 T cell receptor-immunoglobulin chimeric protein:antibody specificity and protection of nonobese diabetic mice against adoptive transfer of diabetes by maternal immunization.

1996 ◽  
Vol 184 (5) ◽  
pp. 1755-1768 ◽  
Author(s):  
U McKeever ◽  
S Khandekar ◽  
J Newcomb ◽  
J Naylor ◽  
P Gregory ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Adoptive Transfer ◽  
Cell Clone ◽  
Nod Mice ◽  
Cell Receptor ◽  
Transfer Model ◽  
Maternal Immunization ◽  
Nonobese Diabetic ◽  
T Cell Clone

The BDC 2.5 T cell clone is specific for pancreatic beta-cell antigen presented by I-Ag7, and greatly accelerates diabetes when injected into 10-21-d-old nonobese diabetic (NOD) mice. The BDC 2.5 T cell receptor (TCR) has been solubilized as a TCR-IgG1 chimeric protein. All NOD mice immunized against BDC 2.5 TCR-IgG1 produced antibodies recognizing TCR C alpha/C beta epitopes that were inaccessible on the T cell surface. 56% of the mice produced antibodies against the BDC 2.5 clonotype that specifically blocked antigen activation of BDC 2.5 cells. We have used the adoptive transfer model of diabetes to demonstrate that maternal immunization with soluble TCR protects young mice from diabetes induced by the BDC 2.5 T cell clone.

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