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Published on: February 28, 2019
Soluble HLA class I antigen secretion by normal lymphocytes: relationship with cell activation and effect of
J A Brieva1, L M Villar, G Leoro
1Servicio de Inmunologia, Hospital Ramón y Cajal, Madrid, Spain.
Insights
Human lymphocytes actively secrete soluble HLA class I proteins upon stimulation. This process involves RNA and protein synthesis, occurring independently of DNA synthesis and interferon-gamma regulation.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- Human Leukocyte Antigen (HLA) class I antigens are typically integral membrane proteins.
- Soluble forms of HLA class I molecules have been detected in various biological samples.
- Previous work identified a predominant soluble HLA class I form in serum and spleen, lacking specific polymorphic determinants.
Purpose of the Study:
- To further investigate the secretion of soluble HLA class I proteins by lymphocytes.
- To determine the cellular and molecular requirements for sHLA I secretion.
- To explore the regulation of sHLA I secretion in response to different stimuli.
Main Methods:
- Stimulation of normal lymphocytes with phytohaemagglutinin, mitogens, antigens, and alloantigens.
- Analysis of sHLA I secretion kinetics relative to DNA synthesis.
- Investigation of the effects of interferon-gamma on sHLA I secretion.
- Detection of sHLA I secretion in lymphocytes from in vivo-activated subjects.
Main Results:
- Phytohaemagglutinin-stimulated lymphocytes secrete significant quantities of soluble HLA class I (sHLA I) proteins.
- Both T and B lymphocytes secrete sHLA I upon activation, indicating a general lymphocyte property.
- Secretion requires RNA and protein synthesis but not DNA synthesis, with peak secretion preceding DNA synthesis.
- In vitro and in vivo activation of lymphocytes leads to enhanced sHLA I secretion.
- Interferon-gamma does not induce sHLA I secretion, suggesting distinct regulatory pathways.
Conclusions:
- Human lymphocytes actively secrete considerable amounts of soluble HLA class I proteins upon stimulation.
- The secretion mechanism is distinct from the regulation of membrane-bound HLA class I antigens.
- Soluble HLA class I proteins represent a biologically relevant secreted molecule from activated lymphocytes.
Abstract:
HLA class I antigens are thought to be integral membrane proteins. However, soluble forms of these molecules have been detected. Our laboratory has recently shown that the predominant form of these soluble proteins present in human serum, spleen tissue and culture supernatant of activated lymphocytes exhibits molecular weight and structure similar to classical HLA class I antigens, but lacks HLA A or B polymorphic determinants. In the present study, the secretion of such soluble proteins by lymphocytes has been further explored. Phytohaemagglutinin-stimulated normal lymphocytes secrete considerable quantities of soluble HLA (sHLA) class I proteins. This secretion seems to be a general property of lymphocytes, since activation of T as well as B cells by appropriate mitogens equally induce sHLA I secretion. Lymphocytes require RNA and protein synthesis, but not DNA synthesis, for the secretion to occur. Kinetic studies reveal that maximal sHLA I secretion precedes the peak of DNA synthesis by 24 h. In vitro stimulation with antigens or alloantigens also provokes sHLA I secretion. Moreover, this phenomenon has also been detected for in vivo-activated lymphocytes, as enhanced spontaneous sHLA I secretion was observed in cultures of low-density blastic B and T cells, and of blood lymphocytes obtained from normal subjects who had received a booster immunization 5 days earlier. Interferon-gamma (IFN-gamma) increases the expression of membrane-bound class I antigens but does not induce any sHLA I secretion, suggesting that both molecules are under different regulatory mechanisms. Our results indicate that human lymphocytes, upon stimulation, actively secrete considerable amounts of a soluble form of these biologically relevant proteins.
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