T cell repertoires and competitive exclusion.
Self-renewal is generally thought to play a major role in the maintenance of the T-cell repertoire. Here we develop a set of mathematical models for T-cell activation by peptides on antigen presenting cells (APCs). We show that competition between T cells is inherent to the processes involved in T cells binding APCs. We prove that for each dominant peptide only one T-cell clone can ultimately survive the competition. This is analogous to a classical result from theoretical ecology known as the principle of "competitive exclusion". These findings allow for three main results. First, competitive exclusion during an immune response to antigen implies that the clone(s) with the highest affinity for the dominant peptide(s) will outcompete all others. This allows for a form of "affinity selection". Second, the competition for binding antigen gives rise to regulation of T-cell numbers within a single clone. This allows for a regulated form of T-cell memory when T cells are continuously activated by a persisting antigen. Third, competitive exclusion implies that for each peptide only one T-cell specificity can be maintained in the repertoire. If the T-cell repertoire is largely maintained owing to cross-reactivities with various antigens, competitive exclusion means that the diversity of the T-cell repertoire is limited by the number of antigens stimulating the system. If the cross-reactivities were to involve activation by self antigens this would confirm an earlier result suggesting that the T-cell repertoire is diverse owing to the diversity of the self environment.
Theoretical Biology, Utrecht University, The Netherlands.
R J
RJ
De Boer
A S
AS
Perelson
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000941:Antigens / Q000276:immunology; D001667:Binding, Competitive; D002455:Cell Division / Q000276:immunology; D002999:Clone Cells / Q000276:immunology; D004463:Ecology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D008433:Mathematics; D051379:Mice; D008954:Models, Biological; D010455:Peptides / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000941:Antigens; D010455:Peptides