Article

Tetramer-guided epitope mapping reveals broad, individualized repertoires of tetanus toxin-specific CD4+ T cells and suggests HLA-based differences in epitope recognition.

Benaroya Research Institute at Virginia Mason, 1201 Ninth Avenue, Seattle, WA 98101, USA.
International Immunology (impact factor: 3.41). 12/2007; 19(11):1291-301. DOI:10.1093/intimm/dxm099 pp.1291-301
Source: PubMed

ABSTRACT Tetanus toxoid is a routine positive control antigen for cellular assays. Previous studies identified multiple tetanus toxin (TT) epitopes, including some 'universal' epitopes. However, rigorous HLA-restricted study of tetanus toxoid responses is still lacking. In this study, the tetramer-guided epitope mapping approach was used to identify CD4+ T-cell epitopes within the TT heavy chain restricted by 10 different class II alleles. Of 106 peptides tested, 52 contained epitopes. Response frequencies toward specific epitopes varied, indicating prevalent and rare specificities. Most antigenic peptides (85%) were presented by one or two class II alleles. For peptides presented by three or more alleles, truncation studies revealed that some contained multiple epitopes. These results contrast with the perceived notion that tetanus toxoid responses are dominated by universal CD4+ T-cell epitopes. Rather these results illustrate heterogeneous T-cell responses for different class II alleles and individual-specific variation of the T-cell repertoire.

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Keywords

'universal' epitopes
 
10 different class II alleles
 
CD4+ T-cell epitopes
 
cellular assays
 
class II alleles
 
contained multiple epitopes
 
different class II alleles
 
heterogeneous T-cell responses
 
multiple tetanus toxin
 
perceived notion
 
Previous studies
 
rare specificities
 
Response frequencies
 
rigorous HLA-restricted study
 
routine positive control antigen
 
specific epitopes varied
 
tetanus toxoid responses
 
tetramer-guided epitope
 
truncation studies
 
universal CD4+ T-cell epitopes