A fractal clonotype distribution in the CD8+ memory T cell repertoire could optimize potential for immune responses
UMass Chan Affiliations
Department of PathologyDocument Type
Journal ArticlePublication Date
2003-04-19Keywords
CD8-Positive T-LymphocytesClone 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
Amino Acids, Peptides, and Proteins
Cells
Genetic Phenomena
Hemic and Immune Systems
Pathology
Metadata
Show full item recordAbstract
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.Source
J Immunol. 2003 Apr 15;170(8):3994-4001.
DOI
10.4049/jimmunol.170.8.3994Permanent Link to this Item
http://hdl.handle.net/20.500.14038/38237PubMed ID
12682227Related Resources
ae974a485f413a2113503eed53cd6c53
10.4049/jimmunol.170.8.3994
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