MUTATIONAL ANALYSIS OF THE CD2 CD58 INTERACTION - THE BINDING-SITE FOR CD58 LIES ON ONE FACE OF THE 1ST DOMAIN OF HUMAN CD2/

The adhesion interaction between the immunoglobulin superfamily molecu les CD2 and CD58 (lymphocyte function-associated antigen 3) plays an i mportant role in T cell and natural killer cell interaction with vario us antigen-presenting and target cells. Determination of the solution structure of rat CD2 domain 1 has allowed 2 model of human CD2 domain 1 to be generated, and a series of mutants based on this model have be en made. Residues of domain 1 of human CD2 predicted to be solvent exp osed were substituted with the equivalent residues present in the rat CD2 molecule. The ability of these mutants to mediate rosetting with h uman and sheep erythrocytes was studied. Results show that the binding site of CD2 for both human 2nd sheep CD58 maps to the beta sheet cont aining beta strands CC'C''F and G. Residues K34 and E36 in beta strand C, R48 and K49 in beta strand C', and K91 and N92 in the loop connect ing beta strands F 2nd G are shown to be critical in the interaction. The data support the proposition that the interaction between CD2 and CD58 involves the major beta sheet face of CD2.