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Ecological analysis of antigen-specific CTL repertoires defines the relationship between naïve and immune T-cell populations

Thomas, Paul G., Handel, Andreas, Doherty, Peter C., La Gruta, Nicole L.
Proceedings of the National Academy of Sciences of the United States of America 2013 v.110 no.5 pp. 1839-1844
T-lymphocytes, amino acids, cytotoxicity, data collection, ecology, epitopes, high-throughput nucleotide sequencing, immune response, influenza, nucleoproteins, nucleotide sequences, statistical analysis, viral nonstructural proteins
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 CD8 ⁺ T-cell populations specific for four different influenza-derived epitopes (D ᵇNP ₃₆₆, influenza nucleoprotein amino acid residues 366–374; D ᵇPA ₂₂₄, influenza acid polymerase amino acid residues 224–233; D ᵇPB1-F2 ₆₂, influenza polymerase B 1 reading frame 2 amino acid residues 62–70; K ᵇNS2 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 epitope-specific fashion.