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 leukocytes and dendritic cells, and it is characterized by extensive alternative splicing. We identified 7 different LST1 splice variants in PBMC; thus, 14 LST1 splice variants (LST1/A-LST1/N) have been detected in various cell types. These isoforms code for transmembrane as well as soluble LST1 proteins 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 proliferation 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 data demonstrate the protein expression of LST1 on the cell surface of mononuclear cells, and they show an inhibitory effect on lymphocyte proliferation of two LST1 proteins although they have only a very short amino acid homology.
Rollinger-Holzinger
I
I
Laboratoire de Recherche sur le Cancer et les Maladies du Sang, Luxembourg, USA. i.rollinger@cdnet.lu
Eibl
B
B
Pauly
M
M
Griesser
U
U
Hentges
F
F
Auer
B
B
Pall
G
G
Schratzberger
P
P
Niederwieser
D
D
Weiss
E H
EH
Zwierzina
H
H
D000276:Adjuvants, Immunologic / Q000096:biosynthesis / Q000737:chemistry / Q000502:physiology*; D017398:Alternative Splicing / Q000276:immunology*; D000595:Amino Acid Sequence; D001483:Base Sequence; D001798:Blood Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D008565:Membrane Proteins / Q000096:biosynthesis; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics; D020539:Sequence Analysis, Protein; D014158:Transcription, Genetic / Q000276:immunology; D020298:U937 Cells
D000276:Adjuvants, Immunologic; D001798:Blood Proteins; D007166:Immunosuppressive Agents; D047908:Intracellular Signaling Peptides and Proteins; C093604:LST1 protein, human; D008565:Membrane Proteins; D020033:Protein Isoforms