Immunodominance analysis through interactions of CD8+ T cells and DCs in lymph nodes.
Immunodominance is a common phenomenon observed in multiple epitopes immune systems. Previous studies hypothesize that the competition among CD8+ T cell responses against different epitopes can be used to explain immunodominance. This paper proposes a mathematical model that describes the dynamics of CD8+ T cells primed by antigen-presenting dendritic cells (DCs) in the lymph nodes, and shows that the overall avidity of the interactions between peptide-specific T cells and cognate antigen-bearing DCs may determine the immunodominance. The model suggests the probability that a peptide-specific T cell be immunodominant is proportional to (1) the cognate T cell receptor (TCR) affinity, (2) the number of complexes of cognate peptide and major histocompatibility complex (pMHC) per DC, and (3) the half-life of cognate peptide-specific pMHC. The model predicts a threshold density of pMHC complexes for T cell activation. These observations from the mathematical model are consistent with experimental studies in the open literature. For DC-based vaccine design, the model suggests a strategy of immunotherapy based on the injection of cognate antigen-pulsed DCs.
Wu
Y U
YU
Mechanical, Aerospace, and Biomedical Engineering Department, University of Tennessee, Knoxville, TN 37996, USA.
Xia
Lijin
L
Zhang
Mingjun
M
Zhao
Xiaopeng
X
D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D016056:Immunodominant Epitopes / Q000276:immunology*; D007167:Immunotherapy / Q000379:methods; D008198:Lymph Nodes / Q000276:immunology*; D008285:Major Histocompatibility Complex / Q000276:immunology; D018448:Models, Immunological
D016056:Immunodominant Epitopes