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LST1: a gene with extensive alternative splicing and immunomodulatory function.
I Rollinger-Holzinger1, B Eibl, M Pauly
1Laboratoire de Recherche sur le Cancer et les Maladies du Sang, Luxembourg, USA. i.rollinger@cdnet.lu
Journal of Immunology (Baltimore, Md. : 1950)
|March 8, 2000
Summary
Leukocyte-specific transcript 1 (LST1) proteins are expressed on mononuclear cells and can inhibit lymphocyte proliferation. Two LST1 variants, LST1/C and LST1/A, show distinct structures but similar inhibitory effects.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- The leukocyte-specific transcript 1 (LST1) gene is located in the human MHC TNF region.
- LST1 is constitutively expressed in leukocytes and dendritic cells, exhibiting extensive alternative splicing.
Purpose of the Study:
- To investigate the protein expression and functional effects of LST1 splice variants.
- To characterize the inhibitory impact of LST1 variants on lymphocyte proliferation.
Main Methods:
- Identification of LST1 splice variants in peripheral blood mononuclear cells (PBMC).
- Demonstration of transmembrane LST1 variant LST1/C expression on monocytic cell lines (U937, THP1).
- Assessment of recombinant LST1/C and LST1/A effects on lymphocyte proliferation.
Main Results:
- 14 LST1 splice variants (LST1/A-LST1/N) were detected, coding for transmembrane and soluble proteins.
- Transmembrane LST1/C variant was found on the cell surface of U937 and THP1 cells.
- Both LST1/C and LST1/A variants inhibited lymphocyte proliferation, with LST1/C showing a profound effect.
Conclusions:
- LST1 proteins are expressed on the surface of mononuclear cells.
- Two LST1 variants, despite limited sequence homology, inhibit lymphocyte proliferation.