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Deriving Quantitative Constraints on T Cell Selection from Data on the Mature T Cell Repertoire¹

Vincent Detours^*,,, Ramit Mehr^§ and Alan S. Perelson^2,*

^* Theoretical Biology and Biophysics, and Center for Nonlinear Studies, Los Alamos National Laboratory, Los Alamos NM 87545; Santa Fe Institute, Santa Fe NM 87501; and ^§ Department of Molecular Biology, Princeton University, Princeton, NJ 08544

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 10³–10⁵ self peptides.

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