Threshold detection of self-antigen/MHC class II complexes formed in vivo: constitutive presentation of an immunodominant epitope of hen egg lysozyme (HEL) in HEL-transgenic mice.
Hen egg lysozyme (HEL)-specific T hybridomas were used to study the presentation of HEL as a self component in tolerant, HEL-transgenic mice expressing different serum levels of HEL (AL3, 3-7 nM: ML5, 1-3 nM). Constitutive presentation of the HEL46-61 determinant was detectable in antigen presenting cell (APC)-enriched preparations of spleen, thymus, and lymph node from AL3 transgenic mice. The most likely cell responsible for constitutive presentation of HEL antigen was a non-B cell. In addition, constitutive presentation of HEL46-61 was clearly evident in thymic rosettes (complexes of macrophages or dendritic cells and lymphoid cells) derived from AL3 HEL-transgenic mice, but not from ML5 HEL-transgenic mice. In contrast to the HEL46-61 determinant, constitutive presentation of the HEL25-43 and HEL112-129 determinants was not detectable on APC-enriched preparations from either of the HEL-transgenic lines tested. Thus, although T cell tolerance was evident in transgenic mice expressing a range of serum HEL concentrations, constitutive presentation of processed HEL antigen was not detectable on APCs from mice expressing less than 3-7 nM. This threshold of detectable antigen presentation is consistent with the notion that the concentration of nominal antigen needed for tolerizing T cells is less than that required for activation of mature T cells.
Centre for Transfusion Medicine and Immunology, Flinders Medical Centre, Bedford Park, Australia.
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Kanost
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Basten
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McCluskey
D000818:Animals; D000938:Antigen-Presenting Cells / Q000502:physiology*; D002645:Chickens; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007108:Immune Tolerance; D016056:Immunodominant Epitopes; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009113:Muramidase / Q000235:genetics / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
D000949:Histocompatibility Antigens Class II; D016056:Immunodominant Epitopes; D010446:Peptide Fragments; C066759:hen egg lysozyme peptide (46-61); D009113:Muramidase