Fas-independent apoptosis of activated T cells induced by antibodies to the HLA class I alpha1 domain.

Journal article

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 alpha1 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 alpha1 (B9.12.1), alpha2 (W6/32), or alpha3 (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 alpha1 domain of HLA class I trigger apoptosis of activated T lymphocytes by a pathway which does not involve Fas-ligand.

Authors: Genestier, L; Paillot, R; Bonnefoy-Berard, N; Meffre, G; Flacher, M

• Publication status: Published
• Journal: Blood
• Volume: 90
• Issue: 9
• Pages: 3629-3639
• Publication date: 1997-11-01
• EISSN: 1528-0020
• ISSN: 0006-4971
• Language: English
• Keywords: Humans; T-Lymphocytes; Rats; Signal Transduction; Antibodies; Histocompatibility Antigens Class I; Antigens, CD95; Cells, Cultured; Lymphocyte Activation; Animals; Apoptosis