Th1 clones that suppress IgG2ab specifically recognize an allopeptide determinant comprising residues 435-451 of gamma 2ab.
We have previously reported that gamma 2ab/I-A(d)-specific Th1 clones from BALB/c mice (gamma 2aa, H-2d) mediated a long-lasting, selective suppression of serum IgG2ab levels when transferred to newborn (BALB/c x B10.D2)F1 (gamma 2a/b, H-2d) mice (Bartnes, K. and Hannestad, K. Eur. J. Immunol. 1991. 21: 2365). We here analyze the peptide specificity of hybridomas derived from two suppressive T cell clones. The shortest synthetic peptide with optimal antigenicity comprises gamma 2ab residues 435-451 (Kabat numbering). The determinant core encompasses the gamma 2ab 440-446 (KLRVQKS) sequence which contains an I-A(d) allele-specific motif. Challenge with single amino acid-substituted gamma 2ab 435-447 analogs revealed that residues K440, R442 and K445 which are shared by the autologous and allogeneic gamma 2a, as well as residues Q444 and S446 which represent allogeneic differences, are critical for recognition. We obtained evidence that K440, R442 and Q444 are epitope residues, while K445 and S446 contribute to anchoring of the peptide to I-A(d). Amino acids located outside of the core also influence antigenicity, the most striking effect being a 340-870-fold augmentation of potency when gamma 2ab 437-451 is extended by F436. IgG2ab required processing in order to stimulate the hybridomas. The data support the contention that the Th1 clones specific for Fc of gamma 2ab mediated IgG2ab suppression by cognate interaction with sIgG2ab+ B cells that presented a C gamma 2ab peptide(s) derived from their endogenous Ig on major histocompatibility complex class II. The T cells cross-reacted weakly with peptide 435-451 of the autologous gamma 2aa allotype. This opens the possibility that self-peptides from Ig C regions can target B cells for regulatory interactions with autologous Th cells.
Bartnes
K
K
Department of Immunology, University of Tromsø, Norway.
Rekdal
O
O
Briand
J P
JP
Hannestad
K
K
D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens / Q000235:genetics; D002999:Clone Cells / Q000276:immunology; D000939:Epitopes / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006825:Hybridomas / Q000276:immunology; D007108:Immune Tolerance; D007074:Immunoglobulin G / Q000378:metabolism*; D007142:Immunoglobulin gamma-Chains / Q000235:genetics / Q000276:immunology; D007519:Isoantigens / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010455:Peptides / Q000235:genetics / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D001324:Autoantigens; D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D007142:Immunoglobulin gamma-Chains; D007519:Isoantigens; D010455:Peptides; D011948:Receptors, Antigen, T-Cell