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 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.
Osborn
L
L
Biogen Inc, Cambridge, Massachusetts 02142.
Day
E S
ES
Miller
G T
GT
Karpusas
M
M
Tizard
R
R
Meuer
S C
SC
Hochman
P S
PS
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D018801:CD2 Antigens / Q000276:immunology / Q000378:metabolism*; D018968:CD58 Antigens; D000939:Epitopes; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011485:Protein Binding; D011487:Protein Conformation; D051381:Rats; D016415:Sequence Alignment; D013329:Structure-Activity Relationship
D015703:Antigens, CD; D018801:CD2 Antigens; D018968:CD58 Antigens; D000939:Epitopes; D008562:Membrane Glycoproteins