Genomic organization of the CC chemokine MIP-3 alpha/CCL20/LARC/EXODUS/SCYA20, showing gene structure, splice variants, and chromosome localization

We describe the genomic organization of a recently identified CC chemokine, MIP3 alpha /CCL20 (HGMW-approved symbol SCYA20). The MIP-3 alpha /CCL20 ge ne was cloned and sequenced, revealing a four exon, three intron structure, and was localized by FISK analysis to 2q35-q36. Two distinct cDNAs were id entified, encoding two forms of MIP-3 alpha /CCL20, Ala MLP-3 alpha /CCL20 and Ser MIP-3 alpha /CCL20, that differ by one amino acid at the predicted signal peptide cleavage site. Examination of the sequence around the bounda ry of intron 1 and exon 2 showed that use of alternative splice acceptor si tes could give rise to Ata MIP-3 alpha /CCL20 or Ser MIP-3 alpha /CCL20. Bo th forms of MIP-3cr/CCL20 were chemically synthesized and tested for biolog ical activity. Both flu antigen plus IL-a-activated CD4(+) and CD8(+) T lym phoblasts and cord blood-derived dendritic cells responded to Ser and Ala M IP-3 alpha /CCL20. T lymphocytes exposed only to IL-2 responded inconsisten tly, while no response was detected in naive T lymphocytes, monocytes, or n eutrophils. The biological activity of Ser MIP-3 alpha /CCL20 and Ala MIP-3 alpha /CCL20 and the tissue-specific preference of different splice accept or sites are not yet known. (C) 2001 Academic Press.