Monomeric class I molecules mediate TCR/CD3 epsilon/CD8 interaction on the surface of T cells.
Both CD8 and the TCR bind to MHC class I molecules during physiologic T cell activation. It has been shown that for optimal T cell activation to occur, CD8 must be able to bind the same class I molecule that is bound by the TCR. However, no direct evidence for the class I-dependent association of CD8 and the TCR has been demonstrated. Using fluorescence resonance energy transfer, we show directly that a single class I molecule causes TCR/CD8 interaction by serving as a docking molecule for both CD8 and the TCR. Furthermore, we show that CD3epsilon is brought into close proximity with CD8 upon TCR/CD8 association. These interactions are not dependent on the phosphorylation events characteristic of T cell activation. Thus, MHC class I molecules, by binding to both CD8 and the TCR, mediate the reorganization of T cell membrane components to promote cellular activation.
Block
M S
MS
Department of Immunology, Mayo Graduate and Medical Schools, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
Johnson
A J
AJ
Mendez-Fernandez
Y
Y
Pease
L R
LR
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D017252:CD3 Complex; D016827:CD8 Antigens / Q000378:metabolism*; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D004735:Energy Transfer / Q000276:immunology; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000378:metabolism; D010798:Phycocyanin / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
D015415:Biomarkers; D017252:CD3 Complex; C115335:CD3E protein, human; D016827:CD8 Antigens; C067361:CD8 receptor; D005456:Fluorescent Dyes; D015395:Histocompatibility Antigens Class I; D010446:Peptide Fragments; D010714:Phosphatidylethanolamines; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; C002497:allophycocyanin; D010798:Phycocyanin; D016650:Fluorescein-5-isothiocyanate