LST1: A gene with extensive alternative splicing and immunomodulatory function

The gene of the leukocyte-specific transcript (LST1) is encoded within the TNF region of the human MHC. The LST1 gene is constitutively expressed in l eukocytes and dendritic cells, and it is characterized by extensive alterna tive splicing. We identified 7 different LST1 splice variants in PBMC; thus , 14 LST1 splice variants (LST1/A-LST1/N) have been detected in various cel l types. These isoforms code for transmembrane as well as soluble LST1 prot eins characterized by two alternative open reading frames at their 3' end. We demonstrate the presence of the transmembrane variant LST1/C on the cell surface of the monocytic cell lines U937 and THP1. Recombinant expression of LST1/C permitted its profound inhibitory effect on lymphocyte proliferat ion to be observed. In contrast, the alternative transmembrane variant LST1 /A, the extracellular domain of which shows no amino acid sequence homology to LST1/C exerted a weaker but similar inhibitory effect on PBMC. These da ta demonstrate the protein expression of LST1 on the cell surface of mononu clear cells, and they show an inhibitory effect on lymphocyte proliferation of two LST1 proteins although they have only a very short amino acid homol ogy.