A physiological ligand of positive selection is seen with high specificity.
Positive selection is a process that ensures that peripheral T cells express TCR that are restricted to self-MHC molecules. This process requires both self-MHC and self-peptides. We have recently established a TCR transgenic mouse model (C10.4 TCRtrans+) in which the transgenic TCR was selected on the nonclassical MHC class Ib molecule H2-M3 in conjunction with a physiologically occurring peptide derived from the mitochondrial NADH-dehydrogenase subunit 1 gene (9-mer peptide). Here, the specificity of positive selection of C10.4 TCRtrans+ T cells was examined using a fetal thymic organ culture system. We demonstrated that at low peptide concentrations, shortening the NADH-dehydrogenase subunit 1 gene 9-mer peptide or mutating its surface-exposed side chains severely impaired its ability to induce positive selection. We concluded that under physiological conditions positive selection of C10.4 TCRtrans+ T cells was highly specific and occurred at low epitope densities.
Irion
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Department of Medicine, National Jewish Medical and Research Center, Denver, CO 80206, USA.
Berg
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Staerz
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D000818:Animals; D001324:Autoantigens / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009245:NADH Dehydrogenase / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D009842:Oligopeptides / Q000138:chemical synthesis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D009924:Organ Culture Techniques; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology
D001324:Autoantigens; D018984:Epitopes, T-Lymphocyte; C078177:H2-M3 antigen; D015395:Histocompatibility Antigens Class I; D008024:Ligands; D009842:Oligopeptides; D011948:Receptors, Antigen, T-Cell; D009245:NADH Dehydrogenase