Increased positive selection pressure within the complementarity determining regions of the T-cell receptor β gene in New World monkeys

2011 ◽  
pp. n/a-n/a ◽  
Author(s):  
Takaji Matsutani ◽  
Yoshiki Fujii ◽  
Kazutaka Kitaura ◽  
Satsuki Suzuki ◽  
Yuji Tsuruta ◽  
...  
Keyword(s):  
T Cell ◽  
Positive Selection ◽  
T Cell Receptor ◽  
Selection Pressure ◽  
New World ◽  
Cell Receptor ◽  
New World Monkeys ◽  
Positive Selection Pressure ◽  
Complementarity Determining Regions

Defective T-cell receptor signalling and positive selection of Vav-deficient CD4+CDS+thymocytes

Nature ◽  
1995 ◽  
Vol 374 (6521) ◽  
pp. 474-476 ◽  
Author(s):  
Klaus-Dieter Fischer ◽  
Antanina Zmuidzinas ◽  
Sandra Gardner ◽  
Mariano Barbacid ◽  
Alan Bernstein ◽  
...  
Keyword(s):  
T Cell ◽  
Positive Selection ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Receptor Signalling ◽  
Selection Of

scholarly journals A Kinetic Threshold between Negative and Positive Selection Based on the Longevity of the T Cell Receptor–Ligand Complex

1999 ◽  
Vol 189 (10) ◽  
pp. 1531-1544 ◽  
Author(s):  
Calvin B. Williams ◽  
Deborah L. Engle ◽  
Gilbert J. Kersh ◽  
J. Michael White ◽  
Paul M. Allen
Keyword(s):  
T Cells ◽  
T Cell ◽  
Positive Selection ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Ligand Complex ◽  
Altered Peptide Ligands ◽  
Self Peptides ◽  
Selection Of

We have developed a unique in vivo system to determine the relationship between endogenous altered peptide ligands and the development of major histocompatibility complex class II– restricted T cells. Our studies use the 3.L2 T cell receptor (TCR) transgenic mouse, in which T cells are specific for Hb(64–76)/I-Ek and positively selected on I-Ek plus self-peptides. To this endogenous peptide repertoire, we have individually added one of six well-characterized 3.L2 ligands. This transgenic approach expands rather than constrains the repertoire of self-peptides. We find that a broad range of ligands produce negative selection of thymocytes in vivo. When compared with the in vitro TCR–ligand binding kinetics, we find that these negatively selecting ligands all have a half-life of 2 s or greater. Additionally, one of two ligands examined with no detectable binding to the 3.L2 TCR and no activity on mature 3.L2 T cells (Q72) enhances the positive selection of transgenic thymocytes in vivo. Together, these data establish a kinetic threshold between negative and positive selection based on the longevity of TCR–ligand complexes.

scholarly journals The somatically generated portion of T cell receptor CDR3α contributes to the MHC allele specificity of the T cell receptor

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Philippa Marrack ◽  
Sai Harsha Krovi ◽  
Daniel Silberman ◽  
Janice White ◽  
Eleanor Kushnir ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
Positive Selection ◽  
T Cell Receptor ◽  
T Cell Receptors ◽  
Cell Receptor ◽  
Structural Basis ◽  
Major Histocompatibility ◽  
Cell Receptors ◽  
Histocompatibility Complex

Mature T cells bearing αβ T cell receptors react with foreign antigens bound to alleles of major histocompatibility complex proteins (MHC) that they were exposed to during their development in the thymus, a phenomenon known as positive selection. The structural basis for positive selection has long been debated. Here, using mice expressing one of two different T cell receptor β chains and various MHC alleles, we show that positive selection-induced MHC bias of T cell receptors is affected both by the germline encoded elements of the T cell receptor α and β chain and, surprisingly, dramatically affected by the non germ line encoded portions of CDR3 of the T cell receptor α chain. Thus, in addition to determining specificity for antigen, the non germline encoded elements of T cell receptors may help the proteins cope with the extremely polymorphic nature of major histocompatibility complex products within the species.

scholarly journals Somatic hypermutation of T cell receptor α chain contributes to selection in nurse shark thymus

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Jeannine A Ott ◽  
Caitlin D Castro ◽  
Thaddeus C Deiss ◽  
Yuko Ohta ◽  
Martin F Flajnik ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Somatic Hypermutation ◽  
Cytidine Deaminase ◽  
Cell Receptor ◽  
Antigen Receptors ◽  
Cell Repertoire ◽  
Nurse Shark ◽  
Α Chain ◽  
Complementarity Determining Regions

Since the discovery of the T cell receptor (TcR), immunologists have assigned somatic hypermutation (SHM) as a mechanism employed solely by B cells to diversify their antigen receptors. Remarkably, we found SHM acting in the thymus on α chain locus of shark TcR. SHM in developing shark T cells likely is catalyzed by activation-induced cytidine deaminase (AID) and results in both point and tandem mutations that accumulate non-conservative amino acid replacements within complementarity-determining regions (CDRs). Mutation frequency at TcRα was as high as that seen at B cell receptor loci (BcR) in sharks and mammals, and the mechanism of SHM shares unique characteristics first detected at shark BcR loci. Additionally, fluorescence in situ hybridization showed the strongest AID expression in thymic corticomedullary junction and medulla. We suggest that TcRα utilizes SHM to broaden diversification of the primary αβ T cell repertoire in sharks, the first reported use in vertebrates.

scholarly journals Early Deletion and Late Positive Selection of T-Cells Expressing a Male-Specific Receptor in T-Cell Receptor Transgenic Mice

1990 ◽  
Vol 1 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Hung Sia Teh ◽  
Hiroyuki Kishi ◽  
Bernadette Scott ◽  
Peter Borgulya ◽  
Harald Von Boehmer ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Transgenic Mice ◽  
Positive Selection ◽  
T Cell Receptor ◽  
Interleukin 2 ◽  
Cell Receptor ◽  
Early Expression ◽  
Single Positive ◽  
Selection Of

The ontogeny of T cells in T-cell receptor (TCR) transgenic mice, which express a transgenicαβheterodimer, specific for the male (H-Y) antigen in association with H-2Db, was determined. The transgenicαchain was expressed on about 10% of the fetal thymocytes on day 14 of gestation. About 50% of day-15 fetal thymocytes expressed bothαandβtranschains and virtually all fetal thymocytes expressed the transgenicαβheterodimer by day 17. The early expression of the transgenic TCR on CD4-8-thymocytes prevented the development ofγδcells, and led to accelerated growth of thymocytes and an earlier expression of CD4 and CD8 molecules. Up to day 17, no significant differences in T-cell development could be detected between female and male thymuses. By day 18 of gestation, the male transgenic thymus contained more CD4-8-thymocytes than the female transgenic thymus. The preponderance of CD4-8-thymocytes in the male transgenic thymus increased until birth and was a consequence of the deletion of the CD4+8+thymocytes and their CD4-8+precursors. By the time of birth, the male transgenic thymus contained half the number of cells as the female transgenic thymus. The deletion of autospecific precursor cells in the male transgenic mouse began only at day 18 of gestation, despite the fact that the ligand could already be detected by day 16.The preferential accumulation of CD4-8+T cells, which expressed a high density of the transgenic TCR, occurred only after birth and was .obvious in 6-week-old female thymus. These data support the hypothesis that the positive selection of T cells expressing this transgenic heterodimer may involve two steps, i.e., the commitment of CD4+8+thymocytes to the CD4-8+lineage following the interaction of the transgenic TCR with restricting major histocompatibility molecules, followed by a slow conversion of CD4+8+thymocytes into CD4-8+T cells.In normal mice, the precursors of CD+4+8 and single positive thymocytes have the CD4-8-CD3-J11d+(or M1/69+) phenotype. Because of the early expression of the transgenicαβheterodimer, this population was not detected in adult transgenic mice. All CD4-8-M1/ 69+cells expressed the transgenic receptor associated with CD3 and could be readily grown in media containing T-cell lectins and interleukin 2.

The influence of invariant chain on the positive selection of single T cell receptor specificities

1995 ◽  
Vol 25 (7) ◽  
pp. 1851-1856 ◽  
Author(s):  
Sylvie Tourne ◽  
Naoko Nakano ◽  
Stéphane Viville ◽  
Christophe Benoist ◽  
Diane Mathis
Keyword(s):  
T Cell ◽  
Positive Selection ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Invariant Chain ◽  
Selection Of

scholarly journals Positive selection determines T cell receptor V beta 14 gene usage by CD8+ T cells.

1989 ◽  
Vol 170 (1) ◽  
pp. 135-143 ◽  
Author(s):  
N S Liao ◽  
J Maltzman ◽  
D H Raulet
Keyword(s):  
T Cells ◽  
T Cell ◽  
Positive Selection ◽  
T Cell Receptor ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
Cell Receptor ◽  
Radiation Chimeras ◽  
Gene Usage ◽  
Selection Of

We report here a mAb, 14-2, reactive with TCRs that include V beta 14. The frequency of V beta 14+ T cells varies with CD4 and CD8 subset and is controlled by the H-2 genes. Thus CD8+ T cells from H-2b mice include approximately 2.3% V beta 14+ T cells while CD8+ T cells from mice expressing K kappa include greater than 8% V beta 14+ T cells. In all strains examined, 7-8% of CD4+ T cells express V beta 14. The frequent usage of V beta 14 in CD8+ T cells of K kappa-expressing mice is a result of preferential positive selection of V beta 14+ CD8+ T cells as demonstrated by analysis of radiation chimeras. These studies demonstrate that H-2-dependent positive selection occurs in unmanipulated mice. Furthermore, the results imply that positive selection, and possibly H-2 restriction, can be strongly influenced by a V beta domain, with some independence from the beta-junctional sequence and alpha chain.

scholarly journals Restricting Zap70 Expression to CD4+CD8+ Thymocytes Reveals a T Cell Receptor–dependent Proofreading Mechanism Controlling the Completion of Positive Selection

2003 ◽  
Vol 197 (3) ◽  
pp. 363-373 ◽  
Author(s):  
Xiaolong Liu ◽  
Anthony Adams ◽  
Kathryn F. Wildt ◽  
Bruce Aronow ◽  
Lionel Feigenbaum ◽  
...  
Keyword(s):  
T Cell ◽  
Positive Selection ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Thymocyte Development ◽  
Tcr Signaling ◽  
Novel Approach ◽  
Single Positive ◽  
Tcr Signals

Although T cell receptor (TCR) signals are essential for intrathymic T cell–positive selection, it remains controversial whether they only serve to initiate this process, or whether they are required throughout to promote thymocyte differentiation and survival. To address this issue, we have devised a novel approach to interfere with thymocyte TCR signaling in a developmental stage-specific manner in vivo. We have reconstituted mice deficient for Zap70, a tyrosine kinase required for TCR signaling and normally expressed throughout T cell development, with a Zap70 transgene driven by the adenosine deaminase (ADA) gene enhancer, which is active in CD4+CD8+ thymocytes but inactive in CD4+ or CD8+ single-positive (SP) thymocytes. In such mice, termination of Zap70 expression impaired TCR signal transduction and arrested thymocyte development after the initiation, but before the completion, of positive selection. Arrested thymocytes had terminated Rag gene expression and up-regulated TCR and Bcl-2 expression, but failed to differentiate into mature CD4 or CD8 SP thymocytes, to be rescued from death by neglect or to sustain interleukin 7Rα expression. These observations identify a TCR-dependent proofreading mechanism that verifies thymocyte TCR specificity and differentiation choices before the completion of positive selection.

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