CONSERVATION OF STRUCTURE AND FUNCTION BETWEEN HUMAN AND MURINE IL-16

IL-16 is a proinflammatory cytokine that signals via CD4, inducing che motactic and immunomodulatory responses of CD4(+) lymphocytes, monocyt es, and eosinophils, Comparative analysis of murine and human IL-16 ho mologs could reveal conserved structures that would help to identify k ey functional regions of these cytokines, To that end, we cloned the m urine IL-16 cDNA and found a high degree of amino acid similarity comp aring the predicted murine and human IL-16 precursor proteins (pro-IL- 16), The highest similarity (82.1%) was found in the C-terminal region , which is cleaved from pro-IL-16 to yield biologically active IL-16, Chemotaxis experiments with IL-16 of murine and human origin, using mu rine splenocytes or human T lymphocytes as targets, showed cross-speci es stimulation of motility, Synthetic oligopeptides and anti-peptide A b were produced, based on the sequences of three predicted hydrophilic domains of IL-16 potentially presented in exposed positions, None of these peptides had intrinsic IL-16 bioactivity, but one (corresponding to a hydrophilic C-terminal domain of IL-16) partially displaced bind ing of OKT4 mAb to human lymphocytes, This peptide, and its cognate Ab , also inhibited IL-16 chemoattractant activity for human and murine c ells. These studies demonstrate a high degree of structural and functi onal similarity between human and murine IL-16 and suggest that amino acids in the C terminus are critical for its chemoattractant function, The data suggest cross-species conservation of IL-16 receptor structu res as well, Inhibitory peptides may be useful in disease states where the proinflammatory functions of IL-16 are detrimental to the host.