APCs present A beta(k)-derived peptides that are autoantigenic to type B T cells.
Type B T cells recognize peptide provided exogenously but are ignorant of the same epitope derived from intracellular processing. In this study, we demonstrate the existence of type B T cells to an abundant autologous peptide derived from processing of the I-A(k) beta-chain. T cell hybridomas raised against this peptide fail to recognize syngeneic APC despite abundant presentation of the naturally processed epitope but react in a dose-dependent manner to exogenous peptide. Moreover, these hybridomas respond to Abeta(k) peptide extracted from the surface of I-A(k)-expressing APC. This peptide was isolated from B cell lines where it was found in high abundance; it was also present in lines lacking HLA-DM, but in considerably lower amounts. Therefore, type B T cells exist in the naive repertoire to abundant autologous peptides. We discuss the implications of these findings to the potential biological role of type B T cells in immune responses and autoimmune pathology.
Lovitch
Scott B
SB
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Walters
James J
JJ
Gross
Michael L
ML
Unanue
Emil R
ER
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism; D001324:Autoantigens / Q000008:administration & dosage / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism; D016175:B-Lymphocyte Subsets / Q000145:classification / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000008:administration & dosage / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism; D006825:Hybridomas; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000276:immunology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism
D001324:Autoantigens; D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; C474482:I-A(b) antigen, mouse; C111388:I-Ak antigen; D010446:Peptide Fragments