Related Experiment Videos
Delineation of several DR-restricted tetanus toxin T cell epitopes
S Demotz1, A Lanzavecchia, U Eisel
1Institut de Biochimie, Université de Lausanne, Epalinges, Switzerland.
Abstract:
We have characterized five human T cell clones specific for tetanus toxin. The combination of different techniques allowed us to precisely map two T cell epitopes within fragments 830-843 and 1273-1284 of tetanus toxin, as formally demonstrated by the use of corresponding synthetic peptides. The three other T cell clones were specific for regions 2-602, 604-742, and 865-1315 of tetanus toxin, respectively. The five T cell clones were shown to be restricted to HLA-DR Ag. Furthermore, the allele of HLA-DR utilized by the various epitopes has been determined. The use of HLA-DR-transfected L cells as APC directly demonstrated that two epitopes, one of which represented by fragment 1273-1284, were recognized in association with HLA-DRw52a. For the other three T cell epitopes, the data strongly suggested they were recognized in association with HLA-DR5. Finally, a sixth T cell clone was shown to be specific for tetanus toxoid, the vaccinal preparation of tetanus toxin, and not for other tetanus toxin fragments. This indicated that immunization with tetanus toxoid probably elicits a T cell response directed only in part against native tetanus toxin.
Insights
Researchers mapped key T cell epitopes in tetanus toxin, identifying specific HLA-DR associations. This work clarifies the immune response to tetanus toxin and tetanus toxoid vaccination.
Area of Science:
- Immunology
- Molecular Biology
- Vaccinology
Background:
- Tetanus toxin is a potent neurotoxin and a target for vaccine development.
- Understanding T cell responses to tetanus toxin is crucial for optimizing vaccine efficacy.
Purpose of the Study:
- To characterize human T cell clones specific for tetanus toxin.
- To map T cell epitopes within tetanus toxin.
- To determine the HLA-DR restriction of T cell recognition.
Main Methods:
- Characterization of human T cell clones.
- Epitope mapping using synthetic peptides.
- Analysis of T cell recognition in association with HLA-DR alleles using transfected L cells.
Main Results:
- Two T cell epitopes were precisely mapped to tetanus toxin fragments 830-843 and 1273-1284.
- Five T cell clones were restricted to HLA-DR antigens.
- Two epitopes were recognized in association with HLA-DRw52a, and three with HLA-DR5.
- A sixth T cell clone recognized tetanus toxoid but not other toxin fragments.
Conclusions:
- T cell responses to tetanus toxin are specific and restricted by HLA-DR alleles.
- Tetanus toxoid immunization may elicit a T cell response that only partially targets native tetanus toxin.