Abstract
The human T cell erythrocyte receptor (CD2 antigen) allows thymocytes and mature T cells to adhere to thymic epithelium and target cells through a cell surface protein, LFA-3 (refs 1–6). Monoclonal antibodies recognizing CD2 can either block adhesion or, in certain combinations, induce an antigen-independent T cell activation7–9. We have identified the binding sites for 16 monoclonal antibodies against CD2 by a rapid and generally applicable mutational analysis. The binding sites fall in three discrete regions: antibodies that participate in activation and block erythrocyte adhesion bind to the first region; antibodies that block adhesion bind to the second region; and antibodies that participate in activation but do not block adhesion bind to the third region. A large number of mutations selected for loss of antibody reactivity in the first two regions also weaken the CD2–LFA-3 interaction. Good agreement was observed between mutational lesions blocking LFA-3 binding and lesions blocking binding by activating antibodies, which supports the view that such antibodies induce T cell activation by mimicking the effect of LFA-3 binding. CD2 sequences that participate in LFA-3 binding correspond to immunoglobulin variable region hypervariable sequences when the homologous domains are aligned.
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Peterson, A., Seed, B. Monoclonal antibody and ligand binding sites of the T cell erythrocyte receptor (CD2). Nature 329, 842–846 (1987). https://doi.org/10.1038/329842a0
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DOI: https://doi.org/10.1038/329842a0
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