T cell recognition of bovine ribonuclease. Self/non-self discrimination at the level of binding to the I-Ak molecule.
Bovine RNase A specific T-cell hybridomas were generated to study the recognition of foreign Ag by T lymphocytes. One hybrid, TS12, was shown to recognize RNase in association with I-Ak. This hybridoma required bovine RNase to be processed before recognition. The immunogenic determinant on the RNase molecule recognized by TS12 was localized to the tryptic fragment RNase(40-61). All of the stimulatory ability of this determinant was shown to be contained within the synthetic 14mer RNase(43-56). When this segment of bovine RNase was compared with the self murine sequence, only one amino acid difference was found, a substitution of a proline residue at position 50 for a serine residue. This substitution completely abolishes binding to the I-Ak molecule, as shown by both functional and direct binding assays. This finding shows that self/non-self discrimination not only occurs at the level of the T cell, but also can be caused by an inability of the self peptide to associate with a class II molecule.
Lorenz
R G
RG
Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110.
Tyler
A N
AN
Allen
P M
PM
D000818:Animals; D000911:Antibodies, Monoclonal; D000938:Antigen-Presenting Cells / Q000378:metabolism; D001666:Binding Sites, Antibody; D001667:Binding, Competitive; D002417:Cattle; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000276:immunology* / Q000378:metabolism; D006825:Hybridomas / Q000032:analysis; D007111:Immunity, Cellular; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D012259:Ribonuclease, Pancreatic / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000201:enzymology* / Q000276:immunology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000949:Histocompatibility Antigens Class II; D010446:Peptide Fragments; D012259:Ribonuclease, Pancreatic