Functional and phenotypic evidence for presentation of E alpha 52-68 structurally related self-peptide(s) in I-E alpha-deficient mice.
The Y-Ae mAb and the 1H3.1 TCR-alpha beta (V alpha 1/V beta 6) are two immune receptors specific for I-Ab MHC class II molecules complexed to the 52-68 fragment of the alpha-chain of I-E class II molecules (the E alpha 52-68 peptide). A profound intrathymic negative selection occurs in 1H3.1 TCR transgenic mice in the presence of an I-E alpha transgene. The administration of mAbs to 1H3.1/I-E alpha double-transgenic newborn mice reveals that Y-Ae, but not the isotype-matched anti-I-E Y17 mAb, rescues a significant number of mature (V beta 6highCD4+CD8-) thymocytes and allows the detection of E alpha 52-68-reactive T cells in the periphery. These observations indicate that deletion of autoreactive T cells can be specifically inhibited in vivo by an mAb specific for the deleting self-peptide:self-MHC class II complex. Similar inhibition experiments indicate that C57BL/6 (I-Ab+/I-E alpha-) mice constitutively express an E alpha-independent, Y-Ae-recognizable epitope(s). This finding is confirmed by the phenotypic analysis of mature (MHC class II high) C57BL/6 bone marrow-derived dendritic cells. Collectively, these observations further illustrate the peptide specificity of negative selection and demonstrate that MHC class II-positive cells from unmanipulated C57BL/6 mice that lack a functional I-E alpha gene can assemble one or more self-peptide:I-Ab complexes recognizable by the E alpha 52-68:I-Ab complex-specific Y-Ae mAb.
Viret
C
C
Section of Immunobiology and Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA.
Janeway
C A
CA
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D017951:Antigen Presentation / Q000235:genetics*; D000954:Antigens, Surface / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D007145:Immunoglobulin kappa-Chains / Q000235:genetics; D007274:Injections, Intraperitoneal; D051379:Mice; D008805:Mice, Inbred A; D008806:Mice, Inbred AKR; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000235:genetics; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D019076:Transgenes / Q000276:immunology
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D007145:Immunoglobulin kappa-Chains; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; C117647:antigenic peptide Ealpha52-68