Cross-competition of CD8⁺ T cells shapes the immunodominance hierarchy during boost vaccination

Kastenmuller, W., et al. 2007. J. Exp. Med. 9, 2187-2198

Speaker: 張時斌                                   Time: 13:00~14:00, Dec. 12, 2007

Commentator: 黎煥耀 老師                Place: Room 601

Abstract:

Immunodominance hierarchy of CD8⁺ T cells is a phenomenon that had been observed in T cell responses directed against multiple pathogen-derived epitopes¹. Under this phenomenon, CD8⁺ T cells only selectively respond to a rather small number of epitopes from all the given epitopes to induce different levels of T cell responses. This information is important for both viral infections and boost vaccinations. It is generally believed that many factors are involved in shaping the immunodominance hierarchy, including cross-competition, a competition between CD8⁺ T cells with different specificities for accessing to epitopes expressed on antigen presenting cells². In this study, the authors used a vaccinia virus infection model to investigate whether the immunodominance hierarchy of CD8⁺ T cells occurs during trimming the immune responses against vaccinia virus. They demonstrated that priming of T cells was independent of T cell cross-competition. But in boost vaccination, T cells recognizing determinants from late viral proteins showed a defect in proliferation while T cells specific to early viral determinants became the dominant population. A generally reduced and delayed antigen presentation of late viral proteins and cross-competition by CD8⁺ T cells specific to eiptopes derived from early viral proteins were accounted for this defective proliferation. Collectively, cross-competition between T cells with different specificities is actually an important factor of shaping immunodominance hierarchy during vaccinia virus infection. Finding the importance of cross-competition will help many aspects, especially the strategies of boost vaccinations.

References:

1.         Yewdell, J.W. & Bennink, J.R. Immunodominance in major histocompatibility complex class I-restricted T lymphocyte responses. Annual review of immunology 17, 51-88 (1999).

2.         Kedl, R.M., Kappler, J.W. & Marrack, P. Epitope dominance, competition and T cell affinity maturation. Current opinion in immunology 15, 120-127 (2003).