An artificial T cell stimulating matrix (aTM) is engineered by conjugating T cell stimulating signals to a hydrogel. A) Schematic of aTM made from conjugating Signals 1 and 2 to a hyaluronic acid hydrogel. Attachments of Signal 1 and 2 enable effective T cell stimulation that leads to T cell proliferation, differentiation, and effector function. Receptors bind to ECM hydrogel and also contribute to attachment and T cell signaling. B–D) B6 CD8+ T cell fold expansion measured after 7 d of stimulation of the antigen-specific T cells on the hydrogels with Signals 1 + 2 conjugated or soluble (error bars show s.e.m.; **p < 0.005, n = 4, Student’s t-test, two-tailed) (B), conjugated together or alone (error bars show standard error of the mean (s.e.m.); **p < 0.005, ***p < 0.0005, n = 5–7, one-way ANOVA with Tukey’s post-test) (C), and at varying amounts of Signals 1 + 2, n = 5 (D). E) Day 7 CD8+ T cell fold expansion measured after 7 d of stimulation of the antigen-specific T cells on the aTM. T cells were removed from aTM on the day noted and cultured on TCP until day 7.