Evolution of a Complex T Cell Receptor Repertoire during Primary and Recall Bacterial Infection

Abstract

The mechanisms underlying the genesis and maintenance of T cell memory remain unclear. In this study, we examined the evolution of a complex, antigen-specific T cell population during the transition from primary effector to memory T cells after Listeria monocytogenes infection. T cell populations specific for listeriolysin O (LLO)91–99, the immunodominant epitope recognized by H2-Kd–restricted T lymphocytes, were directly identified in immune spleens using tetrameric H2-Kd–epitope complexes. The T cell receptor (TCR) Vβ repertoire of specific T cells was determined by direct, ex vivo staining with a panel of mAbs. We demonstrate that LLO91–99-specific, primary effector T cell populations have a diverse TCR Vβ repertoire. Analyses of memory T cell populations demonstrated similar TCR diversity. Furthermore, experiments with individual mice demonstrated that primary effector and memory T cells have indistinguishable TCR repertoires. Remarkably, after reinfection with L. monocytogenes, LLO91–99-specific T cells have a narrower TCR repertoire than do primary effector or memory T cells. Thus, our studies show that the TCR repertoire of primary effector T lymphocytes is uniformly transmitted to memory T cells, whereas expansion of memory T cells is selective.

Interleukin-18 gene transfer increases antitumor effects of suicide gene therapy through efficient induction of antitumor immunity

“…The tetramer was then stored at 4°C in PBS (pH 7.4) at a concentration of 1 mg/ml in cocktail containing 0.1 sodium azide, 1 g/ml pepstatin, 1 g/ml leupeptin and 1 g/ml aprotinin. 40 Recombinant adenovirus preparation Replication-defective recombinant adenovirus AdlacZ encoding ␤-galactosidase and AdCD encoding E. coli CD were kindly provided by Dr Hamada (Department of Molecular Biotherapy Research, Cancer Institute, Tokyo, Japan). AdIL18 encoding murine IL-18 were constructed from human adenovirus serotype 5 using homologous recombination.…”

Differences in maintenance of CD8+ and CD4+ bacteria‐specific effector‐memory T cell populations

“…For this reason, experimental models based on the adoptive transfer of TCR-transgenic T cells have been established [4]. Unfortunately, results with monoclonal T cell populations, such as TCR transgenic T cells, cannot always be directly translated to endogenous antigenspecific T cell responses, which are usually characterized by a high degree of TCR polyclonality and functional heterogeneity [5,6]. There is, therefore, a need to establish experimental systems in which the CD4 + T cell compartment can be studied in its full in vivo 'plasticity'.…”

Differing Roles of Inflammation and Antigen in T Cell Proliferation and Memory Generation

“…Tetrameric H2-K d /LLO 91-99 and H2-K d /p60 217-225 complexes were generated as recently described (10,35). Briefly, recombinant H2-K d heavy chain and ␤ 2 -microglobulin were expressed as insoluble inclusion bodies in Escherichia coli and were further purified.…”

“…with a sublethal dose of this Gram-positive, intracellular bacterium rapidly clear the pathogen and develop long-lasting immunity, which is predominantly mediated by CD8 ϩ T cells (26,27). Four different Listeria epitopes that are presented by the H2-K d MHC class Ia molecule have been identified (12,28,29), and the kinetics of epitope generation and presentation (28) and the in vivo kinetics of the T cell response have been measured (10,25,30). The immunodominant epitopes LLO 91-99 (listeriolysin O) 4 (derived from the secreted virulence factor listeriolysin (31)) and p60 217-225 (derived from the mureine hydrolase p60 (32)) elicit large epitopespecific T cell populations.…”