CD4 stability is dependent on TCR:MHCII contacts. Irradiated 129 mice were reconstituted with B6 RFP⁺ CD4 cells, unlabeled B6 CD8 cells, and 1:1 mix of CD11c-YFP/MHCII^−/− BM and wt B6 BM or CD11c-YFP BM and B6 MHCII^−/− BM. Shown in panel A are cumulative interaction times between CD4 cells and the YFP⁺ surface (of CD4 cells that ever contact the YFP surface). P = .67 comparing interactions between CD4 cells and wt or MHCII^−/− DCs. (B-C) In vivo treatment with an anti-MHCII mAb (Y3P) increased CD4 cell speeds. (B) Experimental design. (C) Representative images from videos of an ear pre- and posttreatment with Y3P or isotype (supplemental Videos 9-12). (D) Mean CD4 speeds pre- and posttreatment with Y3P (upper panel) or isotype (lower panel). P ≤ .005 comparing speeds before and after Y3P for each mouse. P ≥ .09 comparing speeds before and after isotype antibody treatment of each mouse.