Amino acid residues required for binding of lymphocyte function-associated antigen 3 (CD58) to its counter-receptor CD2

• Published in: The Journal of experimental medicine 1995-01, Vol.181 (1), p.429-434
• Main Authors: Osborn, L, Day, E S, Miller, G T, Karpusas, M, Tizard, R, Meuer, S C, Hochman, P S
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Antigens, CD - metabolism; CD2 Antigens - immunology; CD2 Antigens - metabolism; CD58 Antigens; Epitopes; Humans; Membrane Glycoproteins - metabolism; Models, Molecular; Molecular Sequence Data; Mutagenesis, Site-Directed; Protein Binding; Protein Conformation; Rats; Sequence Alignment; Structure-Activity Relationship
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.181.1.429

Efficient activation and regulation of the cellular immune response requires 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 killer cells of the human immune system. The binding site of human CD2 for LFA-3 has been localized to two epitopes on one face of the first immunoglobulin (Ig)-like domain of this two-domain, Ig superfamily molecule. Human LFA-3 is genetically linked and is 21% identical in amino acid sequence to CD2, suggesting that this adhesive pair may have evolved from a single ancestral molecule. We have aligned the amino acid sequences 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 binding 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.