Physiologically, TCR signaling is unlikely to result from the cross- linking of TCR-CD3 complexes, given the low density of specific peptide-MHC complexes on antigen-presenting cells. We therefore have tested directly an alternative model for antigen recognition. We show that monomers of soluble peptide-MHC trigger Ca2+ responses in CD8αβ+ T cells. This response is not observed in CD8- T cells and when either the CD8:MHC or CD8:Lck interactions are prevented. This demonstrates that an intact CD8 coreceptor is necessary for effective TCR signaling in response to monomeric peptide- MHC molecules. We propose that this heterodimerization of TCR and CD8 by peptide-MHC corresponds to the physiological event normally involved during antigen-specific signal transduction.
Delon, J., Grégoire, C., Malissen, B., Darche, S., Lemaître, F., Kourilsky, P., … Trautmann, A. (1998). CD8 expression allows T cell signaling by monomeric peptide-MHC complexes. Immunity, 9(4), 467–473. https://doi.org/10.1016/S1074-7613(00)80630-5