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

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).

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-A^u involves contacts with both chains of the MHC molecule. In contrast, qCII85.33 TCR recognition of an allopeptide:I-A^u complex appears to predominantly involve the β chain of the MHC molecule. Thus, the two TCR appear to have different footprints on the I-A^u molecules. Unexpectedly, this differential involvement of the two chains of the I-A^u 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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Contributors

Author: E. Sally Ward

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