Surrogate thyroglobulin receptors and T cell proliferation in Hashimoto's thyroiditis.

Abstract

Immunoglobulin molecules on the surface of a B lymphocyte are the endogenous "receptors" to which specific antigens bind. Studies in mice have shown that a monoclonal antibody, conjugated with palmitate to provide a lipid tail, can be inserted into the cell membrane to provide a "surrogate" antigen receptor. We have investigated whether a palmitate conjugate of a human monoclonal antibody specific for thyroglobulin (TG) could function as a surrogate TG receptor on blood mononuclear cells separated into fractions enriched for T cells or depleted of T cells (non-T cells). Using flow cytometry, we detected surrogate TG receptors on non-T (but not on T) cells from 11 of 11 individuals studied (5 Hashimoto patients and 6 control donors). In contrast, endogenous TG receptors could only be detected on non-T cells from 1 of 3 Hashimoto patients and from 0 of 4 control donors. Because of the efficient binding of TG by surrogate receptors on non-T cells, we assessed the ability of such cells to present TG to T cells. Proliferation in response to TG was observed in T cells from only 1 of 5 Hashimoto patients. This low frequency of response was no different from that previously detected using cultures of T cells and autologous dendritic cells. Therefore, the successful generation of surrogate receptors on non-T cells is not associated with more efficient TG presentation of T cells. Furthermore, the significance of the present study is that the T cells, not the antigen-presenting cells, are likely to be the limiting element in the T cell proliferative response to TG and other thyroid autoantigens.

• Authors: N Fukuma, T Hoy, D I Phillips, S M McLachlan
• Journal: Thyroid : official journal of the American Thyroid Association (Thyroid) Vol. 2 Issue 4 Pg. 291-7 ( 1992) ISSN: 1050-7256 [Print] United States
• PMID: 1493370 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Fluorescent Dyes
• Palmitic Acids
• Receptors, Cell Surface
• Receptors, Thyroid Hormone
• thyroglobulin receptor
• Palmitic Acid
• Thyroglobulin
• Fluorescein-5-isothiocyanate

Topics

• Antibodies, Monoclonal (metabolism)
• Cell Division (drug effects)
• Cell Membrane (immunology)
• Female
• Flow Cytometry
• Fluorescein-5-isothiocyanate
• Fluorescent Dyes
• Humans
• Leukocytes, Mononuclear (immunology)
• Male
• Palmitic Acid
• Palmitic Acids
• Receptors, Cell Surface
• Receptors, Thyroid Hormone (analysis, metabolism)
• T-Lymphocytes (pathology)
• Thyroglobulin (immunology, metabolism, pharmacology)
• Thyroiditis, Autoimmune (blood)