scholarly journals Restricted Usage of T Cell Receptor Vα/Jα Gene Segments with Different Nucleotide but Identical Amino Acid Sequences in HLA-DR3+ Sarcoidosis Patients

1995 ◽  
Vol 1 (3) ◽  
pp. 287-296 ◽  
Author(s):  
Johan Grunewald ◽  
Thomas Hultman ◽  
Anders Bucht ◽  
Anders Eklund ◽  
Hans Wigzell
Keyword(s):  
Amino Acid ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Amino Acid Sequences ◽  
Identical Amino Acid ◽  
Hla Dr3

P134 Amino acid sequences of T cell receptor reacting against multiple myeloma

Blood Reviews ◽  
2007 ◽  
Vol 21 ◽  
pp. S129
Author(s):  
S. Dudova ◽  
L. Kovarova ◽  
R. Horvath ◽  
M. Penka ◽  
R. Hajek ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Amino Acid ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Amino Acid Sequences

scholarly journals Evidence of T cell receptor β-chain patterns in inflammatory and noninflammatory bowel disease states

1999 ◽  
Vol 276 (3) ◽  
pp. G613-G621 ◽  
Author(s):  
Lawrence J. Saubermann ◽  
Christopher S. J. Probert ◽  
Andreas D. Christ ◽  
Andreas Chott ◽  
Jerrold R. Turner ◽  
...  
Keyword(s):  
Amino Acid ◽  
T Cell ◽  
T Cell Receptor ◽  
Bowel Disease ◽  
Complex Molecule ◽  
Major Histocompatibility Complex Molecule ◽  
Cell Receptor ◽  
Amino Acid Sequences ◽  
Intestinal Lymphocytes ◽  
Β Chain

T cell activation, as defined by expression of relevant cell surface molecules, such as the interleukin-2 receptor (CD25), is increased in many chronic relapsing diseases, including inflammatory bowel disease (IBD). These T cells are generally activated through contact of their clonotypic T cell receptor (TCR) with a peptide antigen presented by a major histocompatibility complex molecule. One of the putative antigenic contact sites for the TCR is the third complementarity determining region (CDR3) of the TCR β-chain variable region (TCRBV). Therefore, analysis of the TCRBV CDR3 provides insight into the diversity of antigens encountered by a given T cell population. This study evaluated the TCRBV CDR3 usage of the activated intestinal lymphocytes from human subjects with IBD, diverticulitis (inflammatory control), and a normal tissue control. Public patterns, as demonstrated by shared TCRBV CDR3 amino acid sequences of activated intestinal T cell subpopulations, were observed. In particular, a public pattern of TCRBV22, a conserved valine in the fifth position, and use of TCRBJ2S1 or TCRBJ2S5 was present in three of four Crohn’s disease subjects while not present in the ulcerative colitis subjects. However, the private patterns of TCRBV CDR3 region amino acid sequences were far more striking and easily demonstrated in all individuals studied, including a normal noninflammatory control. Thus we conclude that selective antigenic pressures are prevalent among an individual’s activated intestinal lymphocytes.

Developing and validating an approach for diagnosing and prognosticating cancer from biochemical motifs in T-cell receptors.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15260-e15260
Author(s):  
Jared L Ostmeyer ◽  
Lindsay G Cowell ◽  
Scott Christley
Keyword(s):  
Amino Acid ◽  
T Cell ◽  
T Cell Receptor ◽  
T Cell Receptors ◽  
Ovarian Tissue ◽  
Cell Receptor ◽  
Healthy Tissue ◽  
Cervical Lesions ◽  
Cell Receptors ◽  
Biochemical Features

e15260 Background: Immune repertoire deep sequencing allows profiling T-cell populations and enables novel approaches to diagnose and prognosticate cancer by identifying T-cell receptor sequence patterns associated with clinical phenotypes and outcomes. Methods: Our goal is to develop a method to diagnose and prognosticate cancer using sequenced T-cell receptors. To determine how to profile the specificity of a T-cell receptor, we analyze 3D X-ray crystallographic structures of T-cell receptors bound to antigen. We observe a contiguous strip typically 4 amino acid residues in length from the complimentary determining region 3 (CDR3) lying in direct contact with the antigen. Based on this observation, we extract 4 residue long snippets from every receptor’s CDR3 and represent each snippet using biochemical features encoded by its amino acid sequence. The biochemical features are combined with information about the abundance of the snippet or the receptor and scored using a machine learning based approach. Each predictive model is fitted and validated under the requirement that at least one positively labelled snippet appears per tumor and no positively labelled snippets appear in healthy tissue. Results: Using a patient-holdout cross-validation, we fit predictive models to distinguish: 1. colorectal tumors from healthy tissue matched controls with 93% accuracy, 2. breast tumors from healthy tissue matched controls with 94% accuracy, 3. ovarian tumors from non-cancer patient ovarian tissue with 95% accuracy (80% accuracy on a blinded follow-up cohort) 4. and regression of preneoplastic cervical lesions over 1 year in advance with 96% accuracy. Conclusions: Immune repertoires can be used to diagnose and prognosticate cancer.

scholarly journals The presumptive CDR3 regions of both T cell receptor alpha and beta chains determine T cell specificity for myoglobin peptides.

1990 ◽  
Vol 172 (1) ◽  
pp. 27-33 ◽  
Author(s):  
J S Danska ◽  
A M Livingstone ◽  
V Paragas ◽  
T Ishihara ◽  
C G Fathman
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Amino Acid Sequences ◽  
Antigenic Specificity ◽  
Antigenic Peptides ◽  
Surface Complexes ◽  
Receptor Alpha ◽  
Alpha Beta ◽  
Cell Receptor Alpha

The T cell receptor alpha/beta (TCR-alpha/beta) is encoded by variable (V), diversity (D), joining (J), and constant (C) segments assembled by recombination during thymocyte maturation to produce a heterodimer that imparts antigenic specificity to the T cell. Unlike immunoglobulins (Igs), which bind free antigen, the ligands of TCR-alpha/beta are cell surface complexes of intracellularly degraded antigens (i.e., peptides) bound to and presented by polymorphic products of the major histocompatibility complex (MHC). Therefore, antigen recognition by T cells is defined as MHC restricted. A model has been formulated based upon the similarity between TCR-alpha/beta V region and Ig Fab amino acid sequences, and the crystal structure of the MHC class I and Ig molecules. This model predicts that the complementarity determining regions (CDR) 1 and 2, composed of TCR V alpha and V beta segments, primarily contact residues of the MHC alpha helices, whereas V/J alpha and V/D/J beta junctional regions (the CDR3 equivalent) contact the peptide in the MHC binding groove. Because polymorphism in MHC proteins is limited relative to the enormous diversity of antigenic peptides, the TCR may have evolved to position the highly diverse junctional residues (CDR3), where they have maximal contact with antigen bound in the MHC peptide groove. Here, we demonstrate a definitive association between CDR3 sequences in both TCR alpha and beta chains, and differences in recognition of antigen fine specificity using a panel of I-Ed-restricted, myoglobin-reactive T cell clones. Acquisition of these data relied in part upon a modification of the polymerase chain reaction that uses a degenerate, consensus primer to amplify TCR alpha chains without foreknowledge of the V alpha segments they utilize.

scholarly journals Influence of the NH2-terminal Amino Acid of the T Cell Receptor α Chain on Major Histocompatibility Complex (MHC) Class II + Peptide Recognition

1997 ◽  
Vol 185 (11) ◽  
pp. 1919-1927 ◽  
Author(s):  
Jeffrey L. Seibel ◽  
Nancy Wilson ◽  
Haruo Kozono ◽  
Philippa Marrack ◽  
John W. Kappler
Keyword(s):  
Major Histocompatibility Complex ◽  
Amino Acid ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Wild Type ◽  
Terminal Amino Acid ◽  
Histocompatibility Complex ◽  
Terminal Amino ◽  
Α Chain

The α/β T cell receptor (TCR) recognizes peptide fragments bound in the groove of major histocompatibility complex (MHC) molecules. We modified the TCR α chain from a mouse T cell hybridoma and tested its ability to reconstitute TCR expression and function in an α chain–deficient variant of the hybridoma. The modified α chain differed from wild type only in its leader peptide and mature NH2-terminal amino acid. Reconstituted cell surface TCR complexes reacted normally with anti-TCR and anti-CD3 antibodies. Although cross-linking of this TCR with an antibody to the TCR idiotype elicited vigorous T cell hybridoma activation, stimulation with its natural MHC + peptide ligand did not. We demonstrated that this phenotype could be reproduced simply by substituting the glutamic acid (E) at the mature NH2 terminus of the wild type TCR α chain with aspartic acid (D). The substitution also dramatically reduced the affinity of soluble α/β-TCR heterodimers for soluble MHC + peptide molecules in a cell-free system, suggesting that it did not exert its effect simply by disrupting TCR interactions with accessory molecules on the hybridoma. These results demonstrate for the first time that amino acids which are not in the canonical TCR complementarity determining regions can be critical in determining how the TCR engages MHC + peptide.

scholarly journals T Cell Receptor Beta-Chain Profiling of Tumor Tissue, Peripheral Blood and Regional Lymph Nodes From Patients With Papillary Thyroid Carcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Yizeng Wang ◽  
Yuanchao Liu ◽  
Li Chen ◽  
Zuoyu Chen ◽  
Xiaoning Wang ◽  
...  
Keyword(s):  
Amino Acid ◽  
T Cell ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
T Cell Receptor ◽  
Peripheral Blood ◽  
Acid Level ◽  
Amino Acid Level ◽  
Cell Receptor ◽  
Papillary Thyroid

Objective: To study the characteristics of the T cell receptor (TCR) repertoire in cancer tissue, peripheral blood and regional lymph nodes (LNs) from patients with papillary thyroid carcinoma (PTC).Methods: PTC tissue, peripheral blood mononuclear cells (PBMCs) and regional LNs of six patients with papillary thyroid carcinoma were harvested. T cell receptor beta-chain (TCRβ) profiling was performed though high-throughput sequencing (HTS), and IMonitor, MiXCR and VDJtools were used to analyze the characteristics of the TCR repertoire.Results: The results of IMonitor and those of MiXCR and VDJtools were very similar. The unique CDR3 of TCRβ from LNs was higher than that of PBMCs, and the CDR3 of TCRβ from LNs was higher than that of PTC tissue. Shannon's diversity index, D50, inverse Simpson index_mean and normalized Shannon's diversity index_mean of CDR3 from LNs were higher than those of PTCs and PBMCs. The HEC (high expansion clones) rate of CDR3 sequences at the amino acid level in PTC tissue was higher than that of PBMCs, which was higher than that of LNs. The V-J HEC rate of CDR3 was highest in PTC tissue, followed by PBMCs and LNs.Conclusion: TCR CDR3 profiling showed differences among and within the PBMCs, PTC tissues and regional LNs of PTC, including unique CDR3, CDR3 HEC at the amino acid level, CDR3 V-J HEC at the amino acid level, Shannon's diversity index and D50. The TCRβ repertoire of PTC tissue, peripheral blood and regional LNs of PTC provide a reference for further study of immunity mechanisms against PTC.

scholarly journals Antigen experience relaxes the organisational structure of the T cell receptor repertoire

2021 ◽  
Author(s):  
Michal Mark ◽  
Shlomit Reich-Zeliger ◽  
Erez Greenstein ◽  
Dan Reshef ◽  
Asaf Madi ◽  
...  
Keyword(s):  
Amino Acid ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
T Cell Subsets ◽  
Receptor Repertoire ◽  
Adult Mice ◽  
High Level ◽  
T Cell Receptor Repertoire ◽  
Cell Receptor Repertoire

The creation and evolution of the T cell receptor repertoire within an individual combines stochastic and deterministic processes. We systematically examine the structure of the repertoire in different T cell subsets in young, adult and LCMV infected mice, from the perspective of variable gene usage, nucleotide sequences and amino acid motifs. Young individuals share a high level of organization, especially in the frequency distribution of variable genes and amino acid motifs. In adult mice, this structure relaxes and is replaced by idiotypic evolution of the effector and regulatory repertoire. The repertoire of CD4+ regulatory T cells was more similar to naïve cells in young mice, but became more similar to effectors with age. Finally, we observed a dramatic restructuring of the repertoire following infection with LCMV. We hypothesize that the stochastic process of recombination and thymic selection initially impose a strong structure to the repertoire, which gradually relaxes following asynchronous responses to different antigens during life.

scholarly journals T Cell Receptor (TCR) Interacting Molecule (TRIM), A Novel Disulfide-linked Dimer Associated with the TCR–CD3–ζ Complex, Recruits Intracellular Signaling Proteins to the Plasma Membrane

1998 ◽  
Vol 188 (3) ◽  
pp. 561-575 ◽  
Author(s):  
Eddy Bruyns ◽  
Anne Marie-Cardine ◽  
Henning Kirchgessner ◽  
Karin Sagolla ◽  
Andrej Shevchenko ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Amino Acid ◽  
T Cell ◽  
T Cell Receptor ◽  
Intracellular Signaling ◽  
Adaptor Protein ◽  
Cell Receptor ◽  
Sh2 Domain ◽  
Pi3 Kinase ◽  
Signaling Proteins

The molecular mechanisms regulating recruitment of intracellular signaling proteins like growth factor receptor–bound protein 2 (Grb2), phospholipase Cγ1, or phosphatidylinositol 3-kinase (PI3-kinase) to the plasma membrane after stimulation of the T cell receptor (TCR)– CD3–ζ complex are not very well understood. We describe here purification, tandem mass spectrometry sequencing, molecular cloning, and biochemical characterization of a novel transmembrane adaptor protein which associates and comodulates with the TCR–CD3–ζ complex in human T lymphocytes and T cell lines. This protein was termed T cell receptor interacting molecule (TRIM). TRIM is a disulfide-linked homodimer which is comprised of a short extracellular domain of 8 amino acids, a 19–amino acid transmembrane region, and a 159–amino acid cytoplasmic tail. In its intracellular domain, TRIM contains several tyrosine-based signaling motifs that could be involved in SH2 domain–mediated protein–protein interactions. Indeed, after T cell activation, TRIM becomes rapidly phosphorylated on tyrosine residues and then associates with the 85-kD regulatory subunit of PI3-kinase via an YxxM motif. Thus, TRIM represents a TCR-associated transmembrane adaptor protein which is likely involved in targeting of intracellular signaling proteins to the plasma membrane after triggering of the TCR.

Conserved V(D)J junctional sequence of cross-reactive cytotoxic T cell receptor idiotype and the effect of a single amino acid substitution

1991 ◽  
Vol 21 (2) ◽  
pp. 483-488 ◽  
Author(s):  
Toshiyasu Hirama ◽  
Sunao Takeshita ◽  
Yuji Matsubayashi ◽  
Michihiro Iwashiro ◽  
Tohru Masuda ◽  
...  
Keyword(s):  
Amino Acid ◽  
T Cell ◽  
T Cell Receptor ◽  
Amino Acid Substitution ◽  
Cell Receptor ◽  
Single Amino Acid Substitution ◽  
Single Amino Acid ◽  
Cytotoxic T Cell
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