Fas-Independent Apoptosis of Activated T Cells Induced by Antibodies to the HLA Class I a1 Domain

In addition to their major function in antigen presentation shown by DNA fragmentation, phosphatidylserine externalization, and decrease of mitochondrial transmembrane poand natural killer cell activity regulation, HLA class I molecules may modulate T-cell activation and proliferation. tential was observed whatever the type of T-cell activator. Apoptosis did not result from Fas/Fas-L interaction and disMonoclonal antibodies (MoAbs) that recognize distinct epitopes of HLA class I molecules were reported to interfere tinct though partly overlapping populations of activated T cells were susceptible to Fas– and HLA class I–mediated with T-cell proliferation. We show here that two MoAbs (mouse MoAb90 and rat YTH862) that bind to an epitope of apoptosis, respectively. Induction of apoptosis did not require HLA class I cross-linking inasmuch as it could be obthe a1 domain of HLA class I heavy chain induce apoptotic cell death of activated, but not resting, peripheral T lymphoserved with monovalent Fab* fragments. The data indicate that MoAb90 and YTH862 directed against the a1 domain cytes. Other reference anti-HLA class I antibodies specific for distinct epitopes of the a1 (B9.12.1), a2 (W6/32), or a3 of HLA class I trigger apoptosis of activated T lymphocytes by a pathway which does not involve Fas-ligand. (TP25.99) domains of the heavy chain decreased T-cell proliferation but had little or no apoptotic effect. Apoptosis q 1997 by The American Society of Hematology.