Surrogate thyroglobulin receptors and T cell proliferation in Hashimoto's thyroiditis.
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.
Fukuma
N
N
Department of Medicine, University of Wales, College of Medicine, Heath Park, Cardiff.
Hoy
T
T
Phillips
D I
DI
McLachlan
S M
SM
D000911:Antibodies, Monoclonal / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008297:Male; D019308:Palmitic Acid; D010169:Palmitic Acids; D011956:Receptors, Cell Surface; D011988:Receptors, Thyroid Hormone / Q000032:analysis / Q000378:metabolism*; D013601:T-Lymphocytes / Q000473:pathology*; D013954:Thyroglobulin / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D013967:Thyroiditis, Autoimmune / Q000097:blood*
D000911:Antibodies, Monoclonal; D005456:Fluorescent Dyes; D010169:Palmitic Acids; D011956:Receptors, Cell Surface; D011988:Receptors, Thyroid Hormone; C032198:thyroglobulin receptor; D019308:Palmitic Acid; D013954:Thyroglobulin; D016650:Fluorescein-5-isothiocyanate