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  • Title: Conversion of low antibody responders into high responders by up-regulating the T cell response to a selective epitope.
    Author: Mikszta JA, Kim BS.
    Journal: J Immunol; 1996 Oct 01; 157(7):2883-90. PubMed ID: 8816393.
    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.
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