Information tracking the size of a TCR transgenic CD4+ T cell clone throughout an acute immune response to pigeon cytochrome c by deep sequencing, suggested that the maximal expansion of that clone depends strongly on the initial quantity of precursor cells [25, 184]. Varying the initial precursor density from three to 3 ?104 cells per mouse the population density following one particular week of proliferation and subsequent contraction was roughly cells, where P0 is number of naive precursors [25]. This difference in clonal expansion came about at a late stage in the response, and was not because of variations in recruitment, simply because prior to day three the fold expansion seemed independent from the precursor density. Applying a six hour pulse of BrdU labeling (see under) it was shown that between day 3 and 5 within the response about 60 of your cells had divided (i.e., picked up BrdU) when the response started with 300 cells, whereas only 20 (day four.5) to 40 (day three.five) on the cells had divided when beginning with 30,000 cells [25, 184]. During this immune response of a single week the fraction of dividing cells declined for both precursor densities more than time, beginning to decline at least around day 4 for the higher density, and about day 5 for the low density. Certainly theJ Theor Biol. Author manuscript; offered in PMC 2014 June 21.De Boer and PerelsonPagepeak of your response occurred earlier when the initial precursor density was greater, and the estimate peak size in the response was well described by [25].NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptThis data was fitted to a mathematical model where cells, just after priming by antigen, differentiate from gradually dividing cells, to quickly proliferating cells, to non-dividing cells, to non-divided mature cells [25]. Within the model, the mature cells in the developmental cascade down-regulate the differentiation of slowly dividing cells into rapidly proliferating cells. This enables for any equivalent initial expansion which is independent from the initial precursor frequency, due to the fact the regulatory mature cells only appear later, and for earlier and improved downregulation of the expansion at significant population sizes [25].Buy69812-51-7 De Boer Perelson [52] have re-analyzed precisely the same information to study no matter whether a mechanism where T cells acquire cognate pMHC complexes from the surface of antigen presenting cells (APCs), thereby rising the loss rate of pMHC, may also be responsible for the tight regulation of T cell expansion more than four orders of magnitude of precursor densities.Mal-amido-PEG8-NHS ester structure During cognate interactions with APCs, CD4+ T cells often acquire various cell surface molecules, which includes the antigen specific pMHC complexes binding the T cell receptors inside the immunological synapse [111, 113, 122, 201, 232, 233].PMID:24670464 This leads to a type of antigen precise competitors involving T cells binding the identical pMHC on the same APCs [122, 236], which would be completely consistent with the observations of Quiel et al. [184] simply because T cells of one more specificity hardly affected the fold expansion. Their observation that growing the antigen concentration, or the density of APCs, enhanced the fold expansion at all precursor densities in a equivalent manner [184], indeed suggest that pMHCs on APCs develop into a limiting resource at all precursor densities tested. Building a straightforward mathematical model implementing this “T cell grazing” mechanism, we showed that this explains the data equally effectively [52]. As a consequence, the Quiel et al. [184] d.
