  The set of T cells that express the same T cell receptor (TCR) sequence
represents a T cell clone. The number of different naive T cell clones in an
organism reflects the number of different T cell receptors (TCRs) arising from
recombination of the V(D)J gene segments during T cell development in the
thymus. TCR diversity and more specifically, the clone abundance distribution
is an important factor in immune function. Specific recombination patterns
occur more frequently than others while subsequent interactions between TCRs
and self-antigens are known to trigger proliferation and sustain naive T cell
survival. These processes are TCR-dependent, leading to clone-dependent thymic
export and naive T cell proliferation rates. Using a mean-field approximation
to the solution of a regulated birth-death-immigration model and a modification
arising from sampling, we systematically quantify how TCR-dependent
heterogeneities in immigration and proliferation rates affect the shape of
clone abundance distributions (the number of different clones that are
represented by a specific number of cells, or "clone counts"). By comparing
predicted clone counts derived from our heterogeneous birth-death-immigration
model with experimentally sampled clone abundances, we show that although
heterogeneity in immigration rates causes very little change to predicted
clone-counts, significant heterogeneity in proliferation rates is necessary to
generate the observed abundances with reasonable physiological parameter
values. Our analysis provides constraints among physiological parameters that
are necessary to yield predictions that qualitatively match the data.
Assumptions of the model and potentially other important mechanistic factors
are discussed.
