Identification of a CD4 domain required for interleukin-16 binding and lymphocyte activation.
Interleukin-16 (IL-16) activates CD4(+) cells, possibly by direct interaction with CD4. IL-16 structure and function are highly conserved across species, suggesting similar conservation of a putative IL-16 binding site on CD4. Comparison of the human CD4 amino acid sequence with that of several different species revealed that immunoglobulin-like domain 4 is the most conserved extracellular region. Potential interaction of this domain with IL-16 was studied by testing murine D4 sequence-based oligopeptides for inhibition of IL-16 chemoattractant activity and inhibition of IL-16 binding to CD4 in vitro. Three contiguous 12-residue D4 region peptides (designated A, B, and C) blocked IL-16 chemoattractant activity, with peptide B the most potent. Peptides A and B were synergistic for inhibition, but peptide C was not. Peptides A and B also blocked IL-16 binding to CD4 in vitro, whereas peptide C did not. CD4, in addition to its known function as a receptor for major histocompatibility complex class II, contains a binding site for IL-16 in the D4 domain. The D4 residues required for IL-16 binding overlap those previously shown to participate in CD4-CD4 dimerization following class II major histocompatibility complex binding, providing a mechanistic explanation for the known function of IL-16 to inhibit the mixed lymphocyte reaction.
Liu
Y
Y
Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
Cruikshank
W W
WW
O'Loughlin
T
T
O'Reilly
P
P
Center
D M
DM
Kornfeld
H
H
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D015704:CD4 Antigens / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D019410:Interleukin-16 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015375:Receptors, Interleukin-2 / Q000037:antagonists & inhibitors; D011994:Recombinant Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity
D015704:CD4 Antigens; D019410:Interleukin-16; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins