THE HUMAN OX40 HOMOLOG - CDNA STRUCTURE, EXPRESSION AND CHROMOSOMAL ASSIGNMENT OF THE ACT35 ANTIGEN

Tissue distribution and expression on mitogen and virally stimulated l ymphocytes render the ACT35 molecule a human lymphocyte activation ant igen which as yet could not be clustered. Expression cloning of the AC T35 antigen from a pCDM8 library of the HUT-102 cell line revealed str ong homology of the cDNA and its encoded protein sequence with the for merly described rat OX40 antigen. The 1.4-kb nucleotide sequence and t he deduced 277-amino acid sequence of the single transmembrane protein were 65% and 63% identical, in human and in rat, respectively. Conser vation included one N-linked glycosylation site and one protein kinase C phosphorylation site. When expressed in COS-1 cells, the cDNA prese nted properties comparable to the native ACT35 antigen and the rat OX4 0 molecule (relative molecular mass 48 000). Thus, the ACT35 protein c orresponds to the hitherto unknown human OX40 antigen and is, therefor e, another member of the tumor necrosis factor/nerve growth factor rec eptor (TNFR/NGFR) family. After applying fluorescence in situ hybridiz ation, the human ACT35/OX40 gene could be mapped to chromosome band 1p 36 and is, thus, linked to the genes for TNFR II and CD30.