The relationship of MHC-peptide binding and T cell activation probed using chemically defined MHC class II oligomers.
A series of novel chemically defined soluble oligomers of the human MHC class II protein HLA-DR1 was constructed to probe the molecular requirements for initiation of T cell activation. MHC dimers, trimers, and tetramers stimulated T cells, as measured by upregulation of the activation markers CD69 and CD25, and by internalization of activated T cell receptor subunits. Monomeric MHC-peptide complexes engaged T cell receptors but did not induce activation. For a given amount of receptor engagement, the extent of activation was equivalent for each of the oligomers and correlated with the number of T cell receptor cross-links induced. These results suggest that formation or rearrangement of a T cell receptor dimer is necessary and sufficient for initiation of T cell signaling.
Cochran
J R
JR
Department of Chemistry, Massachusetts Institute of Technology, Cambridge 02139, USA.
Cameron
T O
TO
Stern
L J
LJ
D015415:Biomarkers; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D015798:HLA-DR1 Antigen / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D009842:Oligopeptides / Q000276:immunology / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000276:immunology; D015398:Signal Transduction
D015415:Biomarkers; D017252:CD3 Complex; D015798:HLA-DR1 Antigen; D009842:Oligopeptides; D015375:Receptors, Interleukin-2