Frequency of epitope-specific naive CD4(+) T cells correlates with immunodominance in the human memory repertoire.
The frequency of epitope-specific naive CD4(+) T cells in humans has not been extensively examined. In this study, a systematic approach was used to examine the frequency of CD4(+) T cells that recognize the protective Ag of Bacillus anthracis in both anthrax vaccine-adsorbed vaccinees and nonvaccinees with HLA-DRB1*01:01 haplotypes. Three epitopes were identified that had distinct degrees of immunodominance in subjects that had received the vaccine. Average naive precursor frequencies of T cells specific for these different epitopes in the human repertoire ranged from 0.2 to 10 per million naive CD4(+) T cells, which is comparable to precursor frequencies observed in the murine repertoire. Frequencies of protective Ag-specific T cells were two orders of magnitude higher in immunized subjects than in nonvaccinees. The frequencies of epitope-specific memory CD4(+) T cells in vaccinees were directly correlated with the frequencies of precursors in the naive repertoire. At the level of TCR usage, at least one preferred Vβ in the naive repertoire was present in the memory repertoire. These findings implicate naive frequencies as a crucial factor in shaping the epitope specificity of memory CD4(+) T cell responses.
Benaroya Research Institute at Virginia Mason, Seattle, WA 98101-2795, USA. bkwok@benaroyaresearch.org
William W
WW
Kwok
Venus
V
Tan
Laurie
L
Gillette
Christopher T
CT
Littell
Michele A
MA
Soltis
Rebecca B
RB
LaFond
Junbao
J
Yang
Eddie A
EA
James
Jonathan H
JH
DeLong
D022122:Anthrax Vaccines / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002469:Cell Separation; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005434:Flow Cytometry; D059811:HLA-DRB1 Chains / Q000276:immunology; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology*; D007156:Immunologic Memory / Q000276:immunology*
D022122:Anthrax Vaccines; D018984:Epitopes, T-Lymphocyte; D059811:HLA-DRB1 Chains; D016056:Immunodominant Epitopes