Structural and functional epitopes of the human adhesion receptor CD58 (LFA‐3)

CD58 (LFA‐3), a heavily glycosylated protein of 40–70 kDa, is expressed on a broad range of hematopoietic and non‐hematopoietic cells. It serves as a physiological ligand of the CD2 receptor, present on T cells and natural killer cells, and plays, thus, an important role in lymphocyte adhesion and T cell activation through CD2. Whereas several epitopes and their respective function are known for CD2, a similarly detailed characterization of CD58 is still lacking. We raised a panel of novel murine monoclonal antibodies (mAb) against recombinant human CD58 and describe here the identification of six structurally and/or functionally distinct epitopes on the CD58 molecule. All epitopes were found to be present in equal numbers on a wide range of CD58⁺ cells, none of them being differentially up‐regulated following cell activation or malignant transformation. Two of these epitopes represent functionally relevant sites, involved in binding of CD58 to CD2 and T cell activation via CD2. One further epitope appears to be selectively involved in CD58‐mediated activation, whereas the other three displayed no functional effects. The new mAb allow for the first time the detection of CD58 in enzyme‐linked immunosorbent assays and immunofluorescence while bound to its receptor CD2 in human serum or on freshly isolated blood cells. Finally, one mAb was found to specifically cross‐react with T11TS, the equivalent of CD58 in sheep.