title: Conversion of low antibody responders into high responders by up-regulating the T cell response to a selective epitope.
abstract: Our previous studies have shown that hen egg-white lysozyme (HEL), structurally modified by diazonium-linked conjugation with a simple hapten such as phosphorylcholine (PC), induces more efficient T cell stimulation than the native Ag in low/non-responder C57BL/6 mice. In the present study, we examined whether such a structural modification could have any effect on the Ab response to native HEL in low- and high-responder mice. Surprisingly, C57BL/6 mice immunized with PC-HEL generated a markedly enhanced anti-HEL Ab response, while high responders failed to exhibit such an enhancement. T cell-proliferative responses to a single epitope, HEL47-61, were enhanced exclusively in the PC-HEL-immunized low/non-responder strain. To directly investigate whether a T cell response to this particular epitope is sufficient to induce anti-HEL Ab, peptide priming experiments were performed. Interestingly, C57BL/6 mice directly primed with HEL47-61 generated strong Ab responses against HEL upon immunization with non-immunogenic native HEL, whereas a different HEL epitope (HEL74-88) failed to induce such responses. Further analyses indicated that HEL47-61 induces strong Th2 (in addition to Th1)-type priming required for the IgG1 Ab response, whereas HEL74-88 stimulates only Th1. These results strongly suggest that individual T cell epitopes within the same protein Ag can induce qualitatively different types of T cell responses and that the up-regulated T cell response to a selective epitope, through altered Ag processing or direct priming, can lead to the conversion of low Ab responders into high responders.
authors.affiliation: Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, IL 60611, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Mikszta
authors.forename: B S
authors.initials: BS
authors.lastname: Kim
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation / Q000235:genetics; D001402:B-Lymphocytes / Q000276:immunology; D002645:Chickens; D000939:Epitopes / Q000276:immunology*; D005260:Female; D006241:Haptens / Q000276:immunology*; D007114:Immunization; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009113:Muramidase / Q000737:chemistry / Q000276:immunology*; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000276:immunology*; D010767:Phosphorylcholine / Q000276:immunology*; D013045:Species Specificity; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D000939:Epitopes; D006241:Haptens; D010446:Peptide Fragments; D010767:Phosphorylcholine; D009113:Muramidase