A fractal clonotype distribution in the CD8+ memory T cell repertoire could optimize potential for immune responses.
The nature of CD8(+) T cell memory is still incompletely understood. We have previously reported that the response to an HLA-A2-restricted influenza-derived peptide results in a complex T cell repertoire. In this study we extend this analysis and describe the repertoire with more rigor. In one individual we defined 141 distinct T cell clonotypes on the basis of the unique DNA sequence of the third complementarity-determining region of the TCR beta-chain. The frequency distribution of the clonotypes is not what is expected of a normal distribution but is characterized by a large low-frequency tail. The existence of a complex population indicates a mechanism for maintaining a large number of Ag-specific clonotypes at a low frequency in the memory pool. Ranking the clonotypes allowed us to describe the population in terms of a power law-like distribution with a parameter of decay of approximately 1.6. If the repertoire is divided into subsets, such as clonotypes that use BJ2.7 or those whose third complementarity-determining region encodes the amino acid sequence IRSS, the clonotype frequencies could also be described by a power law-like distribution. This indicates a self similarity to the repertoire in which smaller pieces are slightly altered copies of the larger piece. The power law-like description is stable with time and was observed in a second individual. The distribution of clonotypes in the repertoire could be mapped onto a polygonal spiral using a recursive algorithm. Self similarity, power laws, and recursive mapping algorithms are associated with fractal systems. Thus, Ag-specific memory CD8 T cell repertoires can be considered as fractal, which could indicate optimized flexibility and robustness.
Naumov
Yuri N
YN
Department of Pathology, University of Massachusetts Medical School, Worchester, MA 01655, USA.
Naumova
Elena N
EN
Hogan
Kevin T
KT
Selin
Liisa K
LK
Gorski
Jack
J
D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D002999:Clone Cells; D003001:Cloning, Molecular; D015169:Colony Count, Microbial / Q000706:statistics & numerical data; D022801:Complementarity Determining Regions / Q000235:genetics / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic / Q000706:statistics & numerical data; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D017709:Fractals; D005822:Genetic Vectors; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory / Q000235:genetics / Q000276:immunology*; D009980:Influenza A virus / Q000235:genetics / Q000276:immunology; D018655:Lymphocyte Count / Q000706:statistics & numerical data; D018448:Models, Immunological; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism / Q000821:virology; D014763:Viral Matrix Proteins / Q000235:genetics / Q000276:immunology
D022801:Complementarity Determining Regions; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014763:Viral Matrix Proteins; C098952:influenza virus membrane protein (58-66)