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An active CD8alpha/pMHCI interaction is required for CD8 single positive thymocyte differentiation

Yoon-Joong Kang1, Xiaosong Wang, Sue-Jane Lin

  • 1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, USA.

European Journal of Immunology
|December 2, 2009
PubMed

Insights

The CD8 coreceptor

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • CD8 coreceptor interaction with peptide-MHCI (pMHCI) is crucial for CD8(+) T cell responses.
  • Mouse CD8alphabeta can interact with pMHCI through CD8alpha- or CD8beta-dominated pathways.
  • The functional significance of these distinct interactions in vivo remains incompletely understood.

Purpose of the Study:

  • To investigate the in vivo functional significance of CD8alphabeta/pMHCI complex formation.
  • To elucidate the roles of CD8alpha- and CD8beta-dominated interactions in T cell development and function.

Main Methods:

  • Generation of transgenic (Tg) mice expressing a variant CD8alphabeta (CD8alpha(m3)beta) that forms only CD8beta-dominated complexes.
  • Analysis of thymic differentiation and CD8(+) single-positive thymocyte populations in Tg mice.
  • Mixed bone marrow chimera experiments comparing Tg CD8(+) T cell developmental capacity with wild-type T cells.

Main Results:

  • Tg mice exhibited sub-optimal thymic differentiation with reduced CD8(+) single-positive thymocytes.
  • Tg CD8(+) T cells showed compromised developmental capacity in competitive chimera settings.
  • Peripheral CD8(+) T cells from Tg mice displayed normal effector function against viral infections.

Conclusions:

  • Full thymocyte differentiation requires CD8 coreceptor activities beyond the CD8beta-dominated interaction.
  • CD8alphaalpha and/or CD8alpha-dominated CD8alphabeta/pMHCI complexes contribute essential activities for thymocyte development.
  • Distinct CD8 coreceptor interactions mediate separate functions in T cell development and peripheral immunity.

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