A fractal clonotype distribution in the CD8+ memory T cell repertoire could optimize potential for immune responses
Department of Pathology
CD8-Positive T-Lymphocytes; Clone Cells; Cloning, Molecular; Colony Count, Microbial; Complementarity Determining Regions; Cytotoxicity Tests, Immunologic; Epitopes, T-Lymphocyte; *Fractals; Genetic Vectors; HLA-A2 Antigen; Humans; Immunologic Memory; Influenza A virus; Lymphocyte Count; Models, Immunological; Peptide Fragments; Receptors, Antigen, T-Cell, alpha-beta; T-Lymphocyte Subsets; T-Lymphocytes, Cytotoxic; Viral Matrix Proteins
Life Sciences | Medicine and Health Sciences
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.
DOI of Published Version
J Immunol. 2003 Apr 15;170(8):3994-4001.
Journal of immunology (Baltimore, Md. : 1950)
Naumov, Yuri N.; Naumova, Elena N.; Hogan, Kevin T.; Selin, Liisa K.; and Gorski, Jack, "A fractal clonotype distribution in the CD8+ memory T cell repertoire could optimize potential for immune responses" (2003). Open Access Articles. 1112.