AMINO-ACID-RESIDUES REQUIRED FOR BINDING OF LYMPHOCYTE FUNCTION-ASSOCIATED ANTIGEN-3 (CD58) TO ITS COUNTER-RECEPTOR CD2

Efficient activation and regulation of the cellular immune response re quires engagement of T cell accessory molecules as well as the antigen -specific T cell receptor. The lymphocyte function-associated antigen (LFA) 3 (CD58)/CD2 accessory pathway, one of the first discovered, has been extensively characterized in terms of structure and function of the CD2 molecule, which is present on all T lymphocytes and natural ki ller cells of the human immune system. The binding site of human CD2 f or LFA-3 has been localized to two epitopes on one face of the first i mmunoglobulin (Ig)-like domain of this two-domain, Ig superfamily mole cule. Human LFA-3 is genetically linked and is 21% identical in amino acid sequence to CD2, suggesting that this adhesive pair may have evol ved from a single ancestral molecule. We have aligned the amino acid s equences of LFA-3 and CD2 and mutagenized selected amino acids in the first domain of LFA-3 that are analogous to those implicated in the bi nding site of CD2. The data show that K30 and K34, in the predicted C- C' loop, and D84, in the predicted F-G loop of LFA-3, are involved in binding to CD2, suggesting that two complementary sites on one face of the first domain of each molecule bind to each other.