Control of MHC Restriction by TCR V
            <sub>α</sub>
            CDR1 and CDR2

Sim, Bee-Cheng; Zerva, Loukia; Greene, Mark I.; Gascoigne, Nicholas R. J.

doi:10.1126/science.273.5277.963

Cited by 145 publications

(112 citation statements)

References 27 publications

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“…Three complementarity-determining regions (CDR1, CDR2 and CDR3) have been defined for each of the two TCR chains. Although challenged by some recent studies [3][4][5][6], the portion of the TCR essentially responsible for interaction with the antigenic peptide has been claimed to lie in the CDR3 loops of the two variable regions [1,[7][8][9][10][11][12]. By definition, part of the CDR3 region is encoded by a given J gene segment [7].…”

Section: Introductionmentioning

confidence: 99%

T‐Cell Receptor BJ Gene Segment Expression in Human Umbilical Cord Blood CD4⁺ and CD8⁺ T‐Cell Subsets

et al. 1997

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Jeddi-Tehrani M, Hodara V, Esin S, Török C, Wigzell H, Andersson R. T-Cell Receptor BJ Gene Segment Expression in Human Umbilical Cord Blood CD4 þ and CD8 þ T-Cell Subsets. Scand J Immunol 1997;46: 520-526 By employing RT-PCR-based technology, followed by Southern-blot analysis, patterns of relative TCR BJ gene segment usage in human CD4 þ and CD8 þ umbilical cord blood T cells (UCT) from ten children were determined in relation to seven recombined TCR BV gene (sub) families (BV 3, 5S1,8,9, 12 and 18). Normal frequency of usage of individual BJ members was observed to be extremely nonrandom. BJ usage in association with each BV was ranked and mean ranking values were calculated for individual BJs. Moreover, BJ family usage and family ranges as well as individual BJ over-representations were determined. In all these aspects of BJ exon expression, CD4 þ and CD8 þ UCT displayed similar distribution patterns. Comparisons of BJ usage in UCT subpopulations and in the adult peripheral blood lymphocyte (PBL) counterparts were performed and many similarities were observed. However, discrepancies in two parameters were recorded; contrary to observations in PBL, individual BJ over-representations were virtually absent in UCT, and significantly less wide BJ family ranges were demonstrated in CD8 þ UCT relative to CD8 þ PBL T cells. These differences support the notion that UCT are in a less dynamic state than are PBL T cells. Hence, despite the fact that PBL T cells are subjected to continuous antigenic challenge, the striking resemblance of PBL and UCT with regard to the overall individual relative usage, ranking, mean ranking and family utilisation of BJ gene segments, irrespective of the choice of recombined BV exons, may suggest a relatively nondiscriminatory role for the BJ gene product in antigen recognition as compared to those encoded by the BV, (N) and BD gene segments.

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Section: Introductionmentioning

confidence: 99%

T‐Cell Receptor BJ Gene Segment Expression in Human Umbilical Cord Blood CD4⁺ and CD8⁺ T‐Cell Subsets

et al. 1997

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“…Independently of the Ag selection process during the course of an immune response, mechanisms involved during thymic selection contribute to limit the TCR repertoire diversity (2,3). Although the mechanisms have not been clearly established (reviewed in Refs.…”

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confidence: 99%

Large TCR Diversity of Virus-Specific CD8 T Cells Provides the Mechanistic Basis for Massive TCR Renewal after Antigen Exposure

Miconnet

Marrau

Farina

et al. 2011

The Journal of Immunology

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Ex vivo analysis of virus-specific CD8 T cell populations by anchored PCR has shown that the CD8 TCR repertoire was less oligoclonal (seven to nine clonotypes per individual epitope) than previously thought. In the current study, TCR diversity was investigated by assessing both the overall TCR β-chain variable regions usage as well as the CDR3 regions in ex vivo-isolated CMV- and EBV-specific CD8 T cells from 27 healthy donors. The average number of clonotypes specific to most single viral epitopes comprised between 14 and 77. Changes in the CD8 TCR repertoire were also longitudinally assessed under conditions of HIV-1 chronic infection (i.e., in patients with suppressed virus replication and after treatment interruption and Ag re-exposure). The results showed that a large renewal (≤80%) of the TRB repertoire occurred after Ag re-exposure and was eventually associated with an increased T cell recognition functional avidity. These results demonstrate that the global CD8 TCR repertoire is much more diverse (≤9-fold) than previously estimated and provide the mechanistic basis for supporting massive repertoire renewal during chronic virus infection and Ag re-exposure.

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“…T he TCR for Ag possesses an innate ability to recognize MHC molecules that are programmed into the TCR at the level of nucleotide sequence (1)(2)(3)(4). However, mature T cells do not respond to self-MHC molecules, but instead recognize Ag as peptides bound to self-MHC molecules on APC.…”

mentioning

confidence: 99%

“…The receptor/ligand pair that has emerged as a master regulator of negative selection in several systems is CD40/CD40 ligand (L). 3 Negative selection of CD4 ϩ T cells by class II MHC molecules is profoundly defective in CD40-or CD40L-null mice (21)(22)(23)(24). Since CD40 stimulation of APC increases the expression of many costimulatory molecules, we have hypothesized that CD40 regulates several costimuli that are required for negative selection (21,25).…”

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confidence: 99%

Requirement for a Complex Array of Costimulators in the Negative Selection of Autoreactive Thymocytes In Vivo

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2001

The Journal of Immunology

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Autoreactive thymocytes can be deleted at an immature stage of their development by Ag-induced apoptosis or negative selection. In addition to Ag, negative selection also requires costimulatory signals from APC. We recently used a fetal thymus organ culture system to show that CD5, CD28, and TNF cooperatively regulate deletion of autoreactive thymocytes. Although these experiments provided strong evidence for the action of several costimulators in negative selection, we wished to demonstrate a role for these molecules in a physiologically natural model where thymocytes are deleted in vivo by endogenously expressed Ags. Accordingly, we examined thymocyte deletion in costimulator-null mice in three models of autoantigen-induced negative selection. We compared CD5−/− CD28−/− mice to CD40L−/− mice, which exhibited a profound block in negative selection in all three systems. Surprisingly, only one of the three models revealed a requirement for the CD5 and CD28 costimulators in autoantigen-induced deletion. These results suggest that an extraordinarily complex array of costimulators is involved in negative selection. We predict that different sets of costimulators will be required depending on the timing of negative selection, the Ag, the signal strength, the APC, and whether Ag presentation occurs on class I or class II MHC molecules.

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Control of MHC Restriction by TCR V _α CDR1 and CDR2

Cited by 145 publications

References 27 publications

T‐Cell Receptor BJ Gene Segment Expression in Human Umbilical Cord Blood CD4⁺ and CD8⁺ T‐Cell Subsets

T‐Cell Receptor BJ Gene Segment Expression in Human Umbilical Cord Blood CD4⁺ and CD8⁺ T‐Cell Subsets

Large TCR Diversity of Virus-Specific CD8 T Cells Provides the Mechanistic Basis for Massive TCR Renewal after Antigen Exposure

Requirement for a Complex Array of Costimulators in the Negative Selection of Autoreactive Thymocytes In Vivo

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Control of MHC Restriction by TCR V α CDR1 and CDR2

Cited by 145 publications

References 27 publications

T‐Cell Receptor BJ Gene Segment Expression in Human Umbilical Cord Blood CD4+ and CD8+ T‐Cell Subsets

T‐Cell Receptor BJ Gene Segment Expression in Human Umbilical Cord Blood CD4+ and CD8+ T‐Cell Subsets

Large TCR Diversity of Virus-Specific CD8 T Cells Provides the Mechanistic Basis for Massive TCR Renewal after Antigen Exposure

Requirement for a Complex Array of Costimulators in the Negative Selection of Autoreactive Thymocytes In Vivo

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Control of MHC Restriction by TCR V _α CDR1 and CDR2

T‐Cell Receptor BJ Gene Segment Expression in Human Umbilical Cord Blood CD4⁺ and CD8⁺ T‐Cell Subsets

T‐Cell Receptor BJ Gene Segment Expression in Human Umbilical Cord Blood CD4⁺ and CD8⁺ T‐Cell Subsets