A simple mathematical model helps to explain the immunodominance of CD8 T cells in influenza A virus infections.
Understanding immunodominance, the phenomenon of epitope-specific T cells expanding in an often distinctly hierarchical fashion, is important for the design of T-cell-based intervention strategies. Several recent studies have investigated immunodominance of H-2D(b)-restricted CD8(+) T cells specific for the nucleoprotein NP366 and acid polymerase PA224 epitopes during influenza A virus infection of C57BL/6 mice. CD8(+) T cells specific for these two epitopes are codominant during primary infection; NP366 dominates during secondary infection. While a number of explanations for this observation have been proposed, none of them can fully account for all the observed data. In this article, we use a simple mathematical model to explain the seemingly inconsistent data. We show that the dynamic interactions between CD8(+) T cells and antigen presentation lead to a situation where CD8(+) T cells are limiting during the initial response whereas antigen is limiting in the secondary response. This "numbers game" between antigen and CD8(+) T cells can reproduce the observed immunodominance of the NP336- and PA224-specific CD8(+) T cells, thereby explaining the reported experimental data.
Handel
Andreas
A
Emory University, Department of Biology, 1510 Clifton Road NE, Atlanta, GA 30322, USA. ahandel@emory.edu
Antia
Rustom
R
D000818:Animals; D017951:Antigen Presentation; D018414:CD8-Positive T-Lymphocytes / Q000821:virology*; D000939:Epitopes / Q000737:chemistry; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry*; D016056:Immunodominant Epitopes / Q000737:chemistry; D009980:Influenza A virus / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008954:Models, Biological; D015233:Models, Statistical; D009713:Nucleotidyltransferases / Q000737:chemistry; D009976:Orthomyxoviridae Infections / Q000378:metabolism / Q000821:virology*; D010446:Peptide Fragments / Q000737:chemistry; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism; D014758:Viral Core Proteins / Q000737:chemistry
D000939:Epitopes; D018984:Epitopes, T-Lymphocyte; D016056:Immunodominant Epitopes; D010446:Peptide Fragments; D014758:Viral Core Proteins; C102366:nucleoprotein (366-374), influenza virus; D009713:Nucleotidyltransferases