The Journal of Immunology, Vol 143, Issue 6 1905-1914, Copyright © 1989 by American Association of Immunologists

ARTICLES

Comparison of phosphorylation and internalization of the antigen receptor/CD3 complex, CD8, and class I MHC-encoded proteins on T cells. Role of intracytoplasmic domains analyzed with hybrid CD8/class I molecules [published erratum appears in J Immunol 1990 Jan 1;144(1):408]

C Boyer, N Auphan, J Gabert, D Blanc, B Malissen and AM Schmitt-Verhulst
Centre d'Immunologie INSERM-CNRS de Marseille-Luminy, France.

We analyzed the phosphorylation and the dynamics of TCR/CD3, CD8 and MHC class I molecules during the activation of a CD8+ cytotoxic T lymphocyte clone and of CD8- T helper hybridomas transfected with the gene coding for the native (J. Gabert, C. Langlet, R. Zamoyska, J.R. Parnes, A.M. Schmitt-Verhulst, and B. Malissen. 1987. Reconstitution of MHC class I specificity by transfer of the T cell receptor and Lyt-2 genes. Cell 50:545) or truncated CD8 alpha molecule. The CD3 components gamma and epsilon and the CD8 alpha subunit were phosphorylated after activation of the CTL clone with the protein kinase C activator PMA. Class I MHC molecules were phosphorylated irrespective of PMA activation. Constitutive phosphorylation of the MHC class I products was found to be intrinsic to the transmembrane/cytoplasmic portion of the molecules because it was transferred to the CD8 alpha hybrid molecules composed of extracellular CD8 and MHC class I transmembrane and intracytoplasmic domains (CD8-e/MHC-t-i). Measurements of the dynamics of these cell surface molecules by using radiolabeled mAb revealed distinct behaviors: TCR/CD3 complex ligand internalization was increased (around 50% after 40 to 60 min) after PMA activation, whereas the ligand of class I MHC molecules was internalized at constant rate irrespective of PMA activation. Ligand bound to native CD8 molecules was poorly internalized, irrespective of the activation of the T cells with PMA. The same ligand bound to the CD8-e/MHC-t-i hybrid molecule was internalized at the same rate as a class I MHC molecule ligand, indicating that the behavior of the hybrid molecule was characteristic of the transmembrane/cytoplasmic portion of MHC class I molecules.

This article has been cited by other articles:

				V. Stove, I. Van de Walle, E. Naessens, E. Coene, C. Stove, J. Plum, and B. Verhasselt Human Immunodeficiency Virus Nef Induces Rapid Internalization of the T-Cell Coreceptor CD8{alpha}{beta} J. Virol., September 1, 2005; 79(17): 11422 - 11433. [Abstract] [Full Text] [PDF]

				Y. Itoh and R. N. Germain Single Cell Analysis Reveals Regulated Hierarchical T Cell Antigen Receptor Signaling Thresholds and Intraclonal Heterogeneity for Individual Cytokine Responses of CD4+ T Cells J. Exp. Med., August 29, 1997; 186(5): 757 - 766. [Abstract] [Full Text] [PDF]

				Z. Cai, H. Kishimoto, A. Brunmark, M. R. Jackson, P. A. Peterson, and J. Sprent Requirements for Peptide-induced T Cell Receptor Downregulation on Naive CD8+ T Cells J. Exp. Med., February 17, 1997; 185(4): 641 - 652. [Abstract] [Full Text] [PDF]