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Fas-Independent Apoptosis of Activated T Cells Induced by Antibodies to the HLA Class I  1 Domain
Laurent Genestier,
Romain Paillot,
Nathalie Bonnefoy-Berard,
Geneviéve Meffre,
Monique Flacher,
David Fèvre,
Yong Jun Liu,
Philippe Le Bouteiller,
Herman Waldmann,
Victor H. Engelhard,
Jacques Banchereau, and
Jean Pierre Revillard
From the Laboratory of Immunology, INSERM U80 UCBL, Hôpital E. Herriot, Lyon, France; Schering-Plough, Laboratory for Immunological Research, Dardilly, France; Laboratory of Immune Response and Major Histocompatibility Complex, INSERM U395, Toulouse, France; Sir William Dunn School of Pathology, University of Oxford, Oxford, UK; and the Department of Microbiology, University of Virginia Center, Charlottesville.
In addition to their major function in antigen presentation and natural killer cell activity regulation, HLA class I molecules may modulate T-cell activation and proliferation. Monoclonal antibodies (MoAbs) that recognize distinct epitopes of HLA class I molecules were reported to interfere with T-cell proliferation. We show here that two MoAbs (mouse MoAb90 and rat YTH862) that bind to an epitope of the  1 domain of HLA class I heavy chain induce apoptotic cell death of activated, but not resting, peripheral T lymphocytes. Other reference anti-HLA class I antibodies specific for distinct epitopes of the 1 (B9.12.1), 2 (W6/32), or 3 (TP25.99) domains of the heavy chain decreased T-cell proliferation but had little or no apoptotic effect. Apoptosis shown by DNA fragmentation, phosphatidylserine externalization, and decrease of mitochondrial transmembrane potential was observed whatever the type of T-cell activator. Apoptosis did not result from Fas/Fas-L interaction and distinct though partly overlapping populations of activated T cells were susceptible to Fas- and HLA class I-mediated apoptosis, respectively. Induction of apoptosis did not require HLA class I cross-linking inasmuch as it could be observed with monovalent Fab' fragments. The data indicate that MoAb90 and YTH862 directed against the 1 domain of HLA class I trigger apoptosis of activated T lymphocytes by a pathway which does not involve Fas-ligand.
Blood, Vol. 90 No. 9 (November 1), 1997:
pp. 3629-3639
© 1997 by The American Society of Hematology.
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