Loss of CD8 and TCR binding to Class I MHC ligands following T cell activation.
The capacity of T cells to bind peptide/MHC ligands changes with T cell development and differentiation. Here we study changes in peptide/MHC multimer binding following T cell activation. Surprisingly, T cell activation caused a marked reduction in specific peptide/MHC Class I multimer binding, which was distinct from transient TCR down-regulation, and was especially dramatic for engagement with low-affinity peptide/MHC ligands. Direct CD8-Class I interactions were also profoundly and rapidly impaired following T cell stimulation, even though surface CD8alpha and CD8beta levels were unchanged after activation, suggesting that decreased CD8 co-receptor binding contributes to this effect. Finally, we show that enzymatic desialylation restores much of the multimer binding on activated T cells, suggesting that altered glycosylation may inhibit TCR/CD8 binding to peptide/MHC ligands. These radical changes in activated T cells' ability to perceive peptide/MHC ligands may contribute to selective outgrowth of clones with high affinity for the stimulatory ligand.
Kao
Charlly
C
Department of Laboratory Medicine and Pathology, Center for Immunology, University of Minnesota, MMC 334, 420 Delaware Street SE, Minneapolis, MN 55455, USA.
Daniels
Mark A
MA
Jameson
Stephen C
SC
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D016827:CD8 Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D006031:Glycosylation; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D010455:Peptides / Q000276:immunology; D011485:Protein Binding / Q000276:immunology
D016827:CD8 Antigens; D015395:Histocompatibility Antigens Class I; D008024:Ligands; D010455:Peptides