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Identification of an alternatively spliced variant of human CD86 mRNA
G Magistrelli1, G Caron, J F Gauchat
1Centre d'Immunologie Pierre Fabre, Saint Julien en Genevois, France.
Abstract:
CD86 is a costimulatory molecule constitutively expressed by human antigen presenting cells which interacts with CD28 and CTLA-4 expressed by T cells. We have recently reported the identification of an alternatively spliced CD86 mRNA variant (CD86deltaTM) characterized by the deletion of exon 6 which encodes for the transmembrane domain. We report here the identification of an alternatively spliced variant (called CD86deltaEC) expressed by nonstimulated human monocytes and characterized by the deletion of exons 4 and 5 which encode for the extracellular V-like and C-like domains, respectively. The activation of monocytes by IFNgamma (i) induces the preferential expression of the transcript encoding for the membrane form and (ii) increases the expression of CD86 and of the accessory molecules CD40, CD49d and CD54. These results suggest that resting human monocytes may constitutively express different forms of CD86 which can then influence the activation of T cells.
Insights
Human monocytes express different forms of CD86, a key costimulatory molecule. These variants, including CD86deltaEC, may influence T cell activation, suggesting a role in immune responses.
Area of Science:
- Immunology
- Molecular Biology
Background:
- CD86 is a costimulatory molecule on antigen-presenting cells interacting with T cell receptors CD28 and CTLA-4.
- Alternative splicing generates CD86 variants, such as CD86deltaTM, lacking the transmembrane domain.
Purpose of the Study:
- To identify and characterize alternatively spliced CD86 variants in human monocytes.
- To investigate the impact of monocyte activation on CD86 expression.
Main Methods:
- Analysis of alternatively spliced CD86 mRNA variants in human monocytes.
- Assessment of CD86 expression and related molecules upon IFN-gamma activation.
Main Results:
- Identification of a novel CD86 variant, CD86deltaEC, lacking extracellular domains, expressed by nonstimulated monocytes.
- IFN-gamma activation promotes the membrane-bound CD86 transcript and upregulates CD86, CD40, CD49d, and CD54 expression.
Conclusions:
- Resting human monocytes express diverse CD86 isoforms.
- These CD86 variants may play a role in modulating T cell activation by antigen-presenting cells.