Ecology is typically thought of as the study of interactions organisms have with each other and their environment and is focused on the distribution and abundance of organisms both within and between environments. On a molecular level, the capacity to probe analogous questions in the field of T-cell immunology is imperative as we acquire substantial datasets both on epitope-specific T-cell populations through high-resolution analyses of T-cell receptor (TCR) use and on global T-cell populations analyzed via high-throughput DNA sequencing. Here, we present the innovative application of existing statistical measures (used typically in the field of ecology), together with unique statistical analyses, to comprehensively assess how the naïve epitope-specific CD8 + cytotoxic T lymphocyte (CTL) repertoire translates to that found following an influenza-virus-specific immune response. Such interrogation of our extensive, cumulated TCR CDR3β sequence datasets, derived from both naïve and immune 114 , and influenza nonstructural protein 2 amino acid residues 114-121), demonstrates that epitope-specific TCR use in an antiviral immune response is the consequence of a complex interplay between the intrinsic characteristics of the naïve cytotoxic T lymphocyte precursor pool and extrinsic (likely antigen driven) influences, the contribution of which varies in an epitopespecific fashion.+ cytotoxic T lymphocytes (CTLs), the clonotypic T-cell receptor (TCR) recognizes "nonself" peptides (p) in complex with "self" class I MHC glycoproteins (MHCI). To recognize and respond to the vast array of novel pMHCI determinants encountered by a given individual (or population), the adaptive immune system uses the recombination of variable (V), junctional (J), diversity (D), and constant (C) somatic gene segments to establish an extraordinary spectrum of TCRs. Most of the observed TCR diversity results from imprecise joining of these gene segments and the addition of nontemplate-encoded nucleotides at V(D)J junctions (1). The consequence is that TCR diversity is principally a function of the CDR3 regions, meaning that clonal uniqueness is reliably defined by the TCRαβ CDR3 sequences.The nature of the highly specific TCR-pMHC recognition event likely determines functional outcomes after T-cell activation (2-6). Thus, the complexity and distribution of TCR use within a responding CTL population is likely to have a very real impact on the efficacy of T-cell-mediated pathogen clearance. Certainly, both virus control and the prevention of mutational escape operate more effectively if the host response is characterized by a diverse, rather than a limited, spectrum of pMHCI-specific TCRs (7-12). Further, TCR diversity has also been associated with effective cross-reactive immunity against different virus infections (13).Single cell RT-PCR analysis of CDR3 nucleotide sequences has provided an unprecedented level of resolution for characterizing TCR use, especially in the case of CTL responses to pathogens. Such detailed dissection of epitope-speci...