Structure-function studies of CD2 by n.m.r. and mutagenesis.

Introduction One of the more familiar examples of cell-cell recognition is that between T cells and an antigenpresenting cell, which consists of a complex array of interprotein interactions that are just beginning to be unravelled [ 1, 21. These interactions promote and support the recognition of foreign antigenic peptides bound to major histocompatibility proteins by specific T-cell receptor molecules. One component of this interface is the adhesion of the T-cell antigen CD2 to lymphocyte function-associated antigen-3 (LFA-3) (in the case of humans) [3 , 41 or to CD48 (in the case of rodents) [S, 61 on the presenting cell. Human CD48 may also be a ligand for human CD2, although with lower affinity than LFA-3 [7]. The extracellular portions of LFA-3, CD2 and CD48 are all predicted to have similar structures [8]. Monoclonal antibodies to CD2 or to LFA-3 can block conjugate formation [9], and certain pairs of anti-CD2 mAbs can effect an antigenindependent stimulation of the T cell, implicating CD2 in a signal-transduction role [lo-121. The adhesion role of CD2 has been shown to be mediated by the first N-terminal domain [ 131. Hefore our structural work on the rat T-cell CD2 antigen, there were conflicting reports in the literature concerning the assignment of the protein to the immunoglobulin superfamily (IgSF) of cellsurface molecules [ 141. Williams and colleagues proposed, on the basis of sequence pattern analysis, that the extracellular portion of the CD2 antigen consisted of two domains with limited similarity to proteins with presumed immunoglobulin-like folds [8, 151. In contrast, an alternative analysis, based on theoretical structure prediction and on limited biophysical studies (including circular dichroism) of the first domain of human 0 2 , led to the proposal