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Activation of a T cell hybridoma by an alloligand results in differential effects on IL-2 secretion and activation-induced cell death

Activation of a T cell hybridoma by an alloligand results in differential effects on IL-2 secretion and activation-induced cell death
Activation of a T cell hybridoma by an alloligand results in differential effects on IL-2 secretion and activation-induced cell death

The molecular nature of the interaction of T cell receptors (TCR) with alloligands is not well understood. Although a role for groove-bound peptide(s) has been clearly demonstrated for major histocompatibility complex (MHC) class I alloreactivity, this has not been established for MHC class II-induced alloresponses. In the present study, we have analyzed the interaction of a nominal peptide-self MHC complex and of an alloligand with their cognate TCR (1934.4 TCR for autoantigen recognition and qCII85.33 TCR for allorecognition). Our results demonstrate that 1934.4 TCR recognition of the N-terminal epitope of myelin basic protein (Ac1-11, Ac=acetylated at position 1) complexed with the MHC class II molecule I-Au involves contacts with both chains of the MHC molecule. In contrast, qCII85.33 TCR recognition of an allopeptide:I-Au complex appears to predominantly involve the β chain of the MHC molecule. Thus, the two TCR appear to have different footprints on the I-Au molecules. Unexpectedly, this differential involvement of the two chains of the I-Au molecule affects activation induced cell death, with allostimulation resulting in poor induction of FasL expression and relatively low levels of apoptosis. Significantly, stimulation of cognate T cells with alloantigen or autoantigen results in similar levels of IL-2 secretion. The reduced apoptosis of T cells in response to allostimulation may be one of the mechanisms that favors the expansion of a relatively large repertoire of alloreactive T cells.

Activation induced cell death, Alloreactivity, TCR-peptide-MHC complex
0014-2980
3825-3832
Qadri, Ayub
c31c2ac2-aaa5-4236-907c-a96dfbc598e8
Ward, E. Sally
b31c0877-8abe-485f-b800-244a9d3cd6cc
Qadri, Ayub
c31c2ac2-aaa5-4236-907c-a96dfbc598e8
Ward, E. Sally
b31c0877-8abe-485f-b800-244a9d3cd6cc

Qadri, Ayub and Ward, E. Sally (2001) Activation of a T cell hybridoma by an alloligand results in differential effects on IL-2 secretion and activation-induced cell death. European Journal of Immunology, 31 (12), 3825-3832. (doi:10.1002/1521-4141(200112)31:12<3825::AID-IMMU3825>3.0.CO;2-O).

Record type: Article

Abstract

The molecular nature of the interaction of T cell receptors (TCR) with alloligands is not well understood. Although a role for groove-bound peptide(s) has been clearly demonstrated for major histocompatibility complex (MHC) class I alloreactivity, this has not been established for MHC class II-induced alloresponses. In the present study, we have analyzed the interaction of a nominal peptide-self MHC complex and of an alloligand with their cognate TCR (1934.4 TCR for autoantigen recognition and qCII85.33 TCR for allorecognition). Our results demonstrate that 1934.4 TCR recognition of the N-terminal epitope of myelin basic protein (Ac1-11, Ac=acetylated at position 1) complexed with the MHC class II molecule I-Au involves contacts with both chains of the MHC molecule. In contrast, qCII85.33 TCR recognition of an allopeptide:I-Au complex appears to predominantly involve the β chain of the MHC molecule. Thus, the two TCR appear to have different footprints on the I-Au molecules. Unexpectedly, this differential involvement of the two chains of the I-Au molecule affects activation induced cell death, with allostimulation resulting in poor induction of FasL expression and relatively low levels of apoptosis. Significantly, stimulation of cognate T cells with alloantigen or autoantigen results in similar levels of IL-2 secretion. The reduced apoptosis of T cells in response to allostimulation may be one of the mechanisms that favors the expansion of a relatively large repertoire of alloreactive T cells.

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More information

Published date: December 2001
Keywords: Activation induced cell death, Alloreactivity, TCR-peptide-MHC complex

Identifiers

Local EPrints ID: 425136
URI: http://eprints.soton.ac.uk/id/eprint/425136
ISSN: 0014-2980
PURE UUID: bed4e86a-2c64-45e5-aaca-d3f25d9e6e26
ORCID for E. Sally Ward: ORCID iD orcid.org/0000-0003-3232-7238

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Date deposited: 11 Oct 2018 16:30
Last modified: 07 Oct 2020 02:22

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Contributors

Author: Ayub Qadri
Author: E. Sally Ward ORCID iD

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