GENOMIC ORGANIZATION AND CHROMOSOMAL LOCALIZATION OF THE T-CELL ANTIGEN 4-1BB

4-1BB is an inducible T cell surface receptor which belongs to the ner ve growth factor receptor superfamily, a group of cysteine-rich cell-s urface proteins. 4-1BB is a 30-kDa glycoprotein and exists as both a m onomer and a 55-kDa dimer on the T cell surface. Cross-linking 4-1BB w ith monoclonal antibody resulted in the 2- to 10-fold enhancement of T cell proliferation. We have isolated and characterized 4-1BB genomic clones and have found that the 4-1BB gene contains two different 5' un translated regions, which are used alternately to form the 4-1BB mRNA. The two 5' UTRs were encoded in the same chromosome and were separate d from one another by an intron of similar to 2.5 kb. The entire gene spans approximately 13 kb of mouse chromosome 4.4-1BB gene consists of 10 exons and 9 introns, in which there are two exons for 5' untransla ted regions and 8 exons for coding region. Most of the putative functi onal domains were encoded by separate exons. 4-1BB extracellular domai n contains four potential C6 (CXn C XX C XX CXn C Xn C) motifs, of whi ch the first motif is partial and the third is distinct from those of nerve growth factor receptor or TNF receptor 1. A comparison of exon-i ntron organization among the genes of the nerve growth factor receptor family indicated that most C6 motif is interrupted by an intron.