title: Dichotomy between the T and the B cell epitopes of the synthetic polypeptide (T,G)-A--L.
abstract: Studies with the well-characterized, synthetic, random-multichain polypeptide poly(LTyr,LGlu)-poly(DLAla)-poly(LLys) (T,G)-A-L) led to the discovery of determinant-specific genetic control of the immune response, as well as to other immunological phenomena. Moreover, the tetrapeptide TyrTyrGluGlu built on the same backbone ("(T-T-G-G)-A--L") was found to represent its major B cell epitope. We have recently shown that for interaction with major histocompatibility complex class II molecules and stimulation of T cells, (T,G)-A--L requires proteolytic processing and the resulting T cell epitopes are close to the N termini of the branched polymer's side chains. Thus, we were interested to elucidate the major T cell epitope of (T,G)-A--L, by using the ordered polypeptides (T-T-G-G)-A--L and (T-G-T-G)-A--L, in which only the two internal amino acids of the tetrapeptide attached to the side chains are switched. We established T cell lines to these antigens, and found that the ordered analog (T-T-G-G-)-A--L, which was defined as the B cell epitope of (T,G)-A--L, did not represent its T cell epitope, whereas (T-G-T-G)-A--L, to which only a minor anti-(T,G)-A--L Ab response was directed, was found to be its major T cell epitope. In addition, there was no cross-reaction between (T-G-T-G)-A--L and (T-T-G-G)-A--L at the T cell level, similar to the lack of cross-reaction of their antibodies. Analysis of the repertoire of the T cell receptors used by these lines revealed that the (T,G)-A--L and the (T-T-G-G)-A--L specific T cell lines were not restricted in their V alpha and V beta TCR usage, whereas the (T-G-T-G)-A--L-specific line was restricted by both V alpha and V beta T cell receptor gene products. This difference might be due to the thymus-independent characteristics previously described for the latter antigen.
authors.affiliation: Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: E
authors.initials: E
authors.lastname: Zisman
authors.forename: M
authors.initials: M
authors.lastname: Sela
authors.forename: A
authors.initials: A
authors.lastname: Ben-Nun
authors.forename: E
authors.initials: E
authors.lastname: Mozes
mesh_terms: D000818:Animals; D000917:Antibody Formation; D000918:Antibody Specificity; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers / Q000737:chemistry; D000939:Epitopes; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D008198:Lymph Nodes / Q000166:cytology; D008213:Lymphocyte Activation; D051379:Mice; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D017931:DNA Primers; D000939:Epitopes; D010455:Peptides; D016693:Receptors, Antigen, T-Cell, alpha-beta; C021759:(T,G)-A-L