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Interactions between the mannose receptor and thyroid autoantigens
G D Chazenbalk1, P N Pichurin, J Guo
1Autoimmune Disease Unit, Cedars-Sinai Research Institute and UCLA School of Medicine, Los Angeles, CA 90048, USA.
Clinical and Experimental Immunology
|January 19, 2005
Summary
The mannose receptor (ManR) may contribute to thyroid autoimmunity by binding to thyroid autoantigens like the TSH receptor and thyroglobulin. This interaction suggests a mechanism for antigen uptake by immune cells in thyroid disease.
Area of Science:
- Immunology
- Endocrinology
- Molecular Biology
Background:
- Thyroid autoantigens must be internalized and processed by antigen-presenting cells to trigger immune responses.
- Receptor-mediated uptake is a key mechanism for antigen presentation, alongside pinocytosis.
- The mannose receptor (ManR) recognizes glycosylated proteins via its carbohydrate recognition domains (CRDs).
Purpose of the Study:
- To investigate the potential role of the mannose receptor (ManR) in thyroid autoimmunity.
- To examine the interaction between ManR and key thyroid autoantigens: TSH receptor (TSHR), thyroid peroxidase (TPO), and thyroglobulin (Tg).
Main Methods:
- Expression and purification of chimeric ManR constructs (CR-Fc and CRD4-7-Fc).
- Enzyme-linked immunosorbent assay (ELISA) to detect binding of chimeric ManRs to immobilized thyroid autoantigens.
- Assessment of calcium dependency, inhibition by mannose/galactose, and requirement for glycosylation in TSHR-ManR interactions.
- Evaluation of the effect of ManR binding on in vitro immune responses of splenocytes from TSHR-immunized mice.
Main Results:
- CRD4-7-Fc exhibited the highest binding to TSHR, followed by Tg, with minimal binding to TPO.
- CR-Fc showed binding to Tg but not to TSHR or TPO.
- TSHR-CRD4-7-Fc interaction was calcium-dependent, inhibited by mannose, and required a glycosylated TSHR A-subunit.
- Precomplexing TSHR A-subunit with CRD4-7-Fc or adding mannose reduced splenocyte responses.
Conclusions:
- The mannose receptor (ManR) likely participates in autoimmune responses against TSHR and Tg, but not TPO.
- ManR binding to glycosylated TSHR A-subunits provides a mechanism for antigen-presenting cells to capture shed thyroid proteins.
- This interaction may be significant in the pathogenesis of thyroid autoimmune diseases.