Deriving quantitative constraints on T cell selection from data on the mature T cell repertoire
被引:28
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作者:
Detours, V
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机构:Univ Calif Los Alamos Natl Lab, Ctr Nonlinear Studies, Los Alamos, NM 87545 USA
Detours, V
Mehr, R
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机构:Univ Calif Los Alamos Natl Lab, Ctr Nonlinear Studies, Los Alamos, NM 87545 USA
Mehr, R
Perelson, AS
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机构:Univ Calif Los Alamos Natl Lab, Ctr Nonlinear Studies, Los Alamos, NM 87545 USA
Perelson, AS
机构:
[1] Univ Calif Los Alamos Natl Lab, Ctr Nonlinear Studies, Los Alamos, NM 87545 USA
[2] Santa Fe Inst, Santa Fe, NM 87501 USA
[3] Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA
来源:
JOURNAL OF IMMUNOLOGY
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2000年
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164卷
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01期
关键词:
D O I:
10.4049/jimmunol.164.1.121
中图分类号:
R392 [医学免疫学];
Q939.91 [免疫学];
学科分类号:
100102 ;
摘要:
The T cell repertoire is shaped in the thymus through positive and negative selection. Thus, data about the mature repertoire may be used to infer information on how TCR generation and selection operate. Assuming that T cell selection is affinity driven, we derive the quantitative constraints that the parameters driving these processes must fulfill to account for the experimentally observed levels of alloreactivity, self MHC restriction and the frequency of cells recognizing a given foreign Ag, We find that affinity-driven selection is compatible with experimental estimates of these latter quantities only if 1) TCRs see more peptide residues than MHC polymorphic residues, 2) the majority of positively selected clones are deleted by negative selection, 3) between 1 and 3.6 clonal divisions occur on average in the thymus after completion of TCR rearrangement, and 4) selection is driven by 10(3)-10(5) self peptides.