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-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 beta 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.
Qadri
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Center for Immunology and Cancer Immunobiology Center, University of Texas Southwestern Medical Center, 6000 Harry Hines Blvd., Dallas, TX 75390-8576, USA.
Ward
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D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D006649:Histocompatibility Antigens / Q000378:metabolism*; D006825:Hybridomas / Q000276:immunology*; D007376:Interleukin-2 / Q000378:metabolism*; D008024:Ligands; D008213:Lymphocyte Activation; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000378:metabolism*; D013601:T-Lymphocytes / Q000502:physiology*
D006649:Histocompatibility Antigens; D007376:Interleukin-2; D008024:Ligands; D011948:Receptors, Antigen, T-Cell