Table I.
All parameters used in ABM simulations. For each parameter, the name, brief description, baseline value and range used for uncertainty and sensitivity analysis is given. Parameter values are based on experimental data or estimated based on related systems and the ability of the model to produce reasonable behavior (calibration) during a chronic infection scenario. For example, recruitment parameters prob_T4_recruitment and prob_T8_recruitment were fixed in order to achieve a ‘normal level’ steady state in the system before infection was introduced. T4 refers to CD4+ T cells, T8 refers to CD8+ T cells.
Parameter | Baseline value | Range | Description | ||
---|---|---|---|---|---|
+* | 1 | pMHC half-life | 60hrs (58) | 30-60 hrs | Half-life of pMHCII on DC |
+* | 2 | unbinding threshold | 100 | 80 – 120 | pMHC level at which T cell unbinds from DC |
+* | 3 | binding threshold | 150 (59, 60) | 100–200 | pMHCII level corresponding to 50% CD4+ T cell binding probability |
+* | 4 | binding shape | 15 | 10-30 | Shape parameter for CD4+ T cell binding probability curve (Fig. 3) |
+* | 5 | priming threshold | 6 hrs (46) | 4 - 8 hrs | Value of pMHC*binding duration at 50% CD4+ T cell priming probability |
+* | 6 | priming shape | 0.6 | 0.3-0.9 | Shape parameter for CD4+ T cell priming probability curve (Fig. 3) |
+* | 7 | binding threshold (CD8 cell) | 200 (11) | 100 - 200 | pMHCI level corresponding to 50% CD8+ T cell binding probability |
+* | 8 | binding shape (CD8 cell) | 15 | 10-30 | Shape parameter for CD8+ T cell binding probability curve (Fig. 3) |
+* | 9 | priming threshold (CD8 cell) | 6 hrs | 4 - 8 hrs | Value of pMHC* binding duration at 50% CD8+ T cells priming probability |
+* | 10 | priming shape (CD8 cell) | 0.6 | 0.3 - 0.9 | Shape parameter for CD8+ T cell priming probability curve (Fig. 3) |
+* | 11 | LDC lifespan | 36 hrs (56, 57) | 24 – 48 hrs | Lifespan of an LDC |
+* | 12 | Prob T4 licenses Ab-DC | 50% | 30 – 80 % | Probability of primed CD4+ T cell licensing Ab-DC |
+ | 13 | Cognate Frequency | 0.25 (see text) | 1:100 – 1:10000 | Frequency of cognate naïve T cells |
+ | 14 | Ab-DC lifespan | 60 hrs (61) | 40 – 80 hrs | Lifespan of an Ab-DC |
+ | 15a | Number of divisions primed CD4+ T cells | 4 (7, 58) | 2 – 8 | Max # of divisions allowed for a primed T cell |
15b | Number of divisions CD8+ T cells | 8 (7) | 2-12 | Max # of divisions allowed for a primed T cell | |
+ | 16 | Division time | 8 hrs | 2 – 16 hrs | Time for primed CD4/CD8 division |
17 | Prob_T4_recruitment | 99% | 50 – 100 % | Probability of naïve CD4+ T cell recruitment at every 20 time steps | |
18 | Prob_T8_recruitment | 95% | 50 – 100 % | Probability of naïve CD8 recruitment at every 20 time steps | |
19 | Initial_naiveT4_cells | 6000 | initial no. of naïve CD4+ T cells | ||
20 | Initial_primedT4_cells | 0 | initial no. of primed CD4+ T cells | ||
21 | Initial_naiveT8_cells | 5000 | initial no. of naïve CD8+ T cells | ||
22 | Initial_primedT8_cells | 0 | initial no. of primed CD8+ T cells | ||
23 | Initial_total DCs_cells | 8 | initial no. of total DCs (IDC+Ab-DC) | ||
24 | %AB-DCs | 60% | percent of total DCs that are antigen bearing | ||
25 | Peak_DCs_level | 100 | Max no. of total DCs on the grid | ||
26 | IDC_Ab-DC_threshold | 50 | pMHC level below which a DC is IDC | ||
27 | n_tcells_bind_DC | 32 | Max no. of T cells that bind to a DC | ||
28 | max_time_T4_primed | 60 hrs (55) | Max time after which primed T4 cells die | ||
29 | max_time_T8_primed | 60 hrs (55) | Max time after which primed T8 cells die | ||
30 | min_T4cell_age | 165 days (54) | Minimum age of naïve T4 when it appears on the grid | ||
31 | max_T4cell_age | 365 days (54) | Maximum age of naïve T4 when it appears on the grid | ||
32 | min_T8cell_age | 165 days (54) | Minimum age of naïve T8 when it appears on the grid | ||
33 | min_T8cell age | 365 days (54) | Maximum age of naïve T8 when it appears on the grid | ||
34 | min_DC_age | 24 hrs (61) | Minimum age of DC when it appears on the grid | ||
35 | max_DC_age | 11 days (61) | Maximum age of DC when it appears on the grid | ||
36 | Initial number of pMHC | taken from a distribution (59, 60) | range 125-200 | Initial number of pMHC placed on surface of DC |
Parameters included in 16 parameter (full) lhs
Parameters included in 12 parameter lhs