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

Eur J Immunol. 2010 Mar;40(3):836-48. doi: 10.1002/eji.200939663.

Abstract

Recognition of viral antigenic peptides bound to major histocompatibility complex class I molecules (MHCI) by TCR is critical for initiating the responses of CD8(+) T cells that ultimately lead to elimination of virus-infected cells. This antigen recognition is enhanced by the CD8 coreceptor through its interaction with the peptide-MHCI complexes (pMHCI). Mouse CD8alphabeta can form two different complexes with pMHCI via either the CD8alpha- or CD8beta-dominated interaction. To understand the functional significance of these complexes in vivo, we generated Tg mice carrying a variant CD8alphabeta (CD8alpha(m3)beta) capable of forming only the CD8beta-dominated CD8alphabeta/pMHCI complex. These mice show sub-optimal thymic differentiation with reduced populations of CD8(+) single-positive thymocytes. Tg CD8(+) T cells exhibit a compromised developmental capacity when competing with CD8(+) T cells from B6 mice in mixed bone marrow chimera experiments. However, once these CD8(+) T cells have emigrated to the peripheral lymphoid organs, they exhibit normal effector function against viral infection. Our observations indicate that, in addition to the CD8 activity conferred by CD8beta-dominated CD8alphabeta/pMHCI complexes, full thymocyte differentiation requires additional coreceptor activities conferred by CD8alphaalpha and/or CD8alphabeta with CD8alpha-dominated CD8/pMHCI complexes.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology
  • CD8 Antigens / immunology*
  • CD8 Antigens / metabolism
  • CD8-Positive T-Lymphocytes / cytology*
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Differentiation / immunology*
  • Cell Separation
  • Flow Cytometry
  • Histocompatibility Antigens Class I / immunology*
  • Histocompatibility Antigens Class I / metabolism
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology
  • Thymus Gland / cytology
  • Thymus Gland / immunology

Substances

  • CD8 Antigens
  • CD8 antigen, alpha chain
  • CD8alphabeta antigen
  • Histocompatibility Antigens Class I