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Two forms of HLA class I molecules in human plasma
1Dana-Farber Cancer Institute, Boston, Massachusetts 02115.
Human Immunology
|October 1, 1987
Summary
Soluble human leukocyte antigen (HLA)-A and -B molecules in plasma exist in two forms: a shed membrane version and a secreted, water-soluble form. This secreted form arises from alternative RNA splicing, similar to in vitro findings.
Area of Science:
- Immunology
- Molecular Biology
- Biochemistry
Background:
- Soluble HLA-A,-B antigens are detected in human plasma.
- In vitro studies show cell lines and lymphocytes secrete soluble HLA molecules via RNA splicing, deleting exon five.
Purpose of the Study:
- To investigate if plasma HLA-A,-B molecules are produced through the same RNA splicing mechanism observed in vitro.
- To biochemically characterize soluble HLA-A,-B molecules found in human plasma.
Main Methods:
- Analysis of molecular weight, lipid binding, and detergent binding properties of plasma HLA-A,-B molecules.
- Comparison of biochemical properties of plasma-derived molecules with in vitro secreted molecules.
Main Results:
- Two distinct forms of soluble HLA-A,-B molecules were identified in plasma: a 43 kd form (shed, binds lipids/detergents) and a 39 kd form (secreted, does not bind lipids/detergents).
- The 39 kd plasma form exhibits identical biochemical properties to HLA molecules secreted in vitro.
- All individuals tested had shed and/or secreted plasma class I molecules, with HLA-A24 notably present in both forms at higher levels than other alleles.
Conclusions:
- Plasma soluble HLA-A,-B molecules likely originate from alternative in vivo RNA splicing events, mirroring in vitro mechanisms.
- The presence of both shed and secreted forms of HLA-A,-B in plasma is common, with specific alleles like HLA-A24 showing distinct expression patterns.