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. Author manuscript; available in PMC: 2019 Mar 6.
Published in final edited form as: Nature. 2018 Sep 5;561(7723):331–337. doi: 10.1038/s41586-018-0499-y

Figure 2 │. Rational-engineering of the Homing System (HS).

Figure 2 │

(A) Cartoon outlining the ALCAM binding-region on CD6, (B) prototype HS-molecule, (C) multimerized exodomains and (D) tailless HSΔ-molecules lacking signaling-domains. (E) Specific binding to soluble ALCAM; assessed independently 10x with similar results. (F) PLA identifying D3/ALCAM heterodimers in T-cell/endothelium-conjugates. 83–103 cell-conjugates analyzed per condition; repeated 3x independently with similar results. TSR=Total Signals-per-Region. (G-J) TEM kinetics of 1×106 cells/condition in microfluidic channels under 1–3dyne/cm2 shear over ALCAM+ pTEC. (K) Transmigration of 2×105 T-cells per well through pTEC cBBB and the effect of soluble ALCAM blockade and washing. Yellow bars show the effect of ALCAM-siRNA knockdown on the permissivity of EC. Three experiments independently performed in triplicates with similar results. All data represented as Mean±SD. P-values represented as *P<0.05, **P<0.01, ***P<0.001. One-way ANOVA then Dunnett’s test for multiple-comparisons (compared to NT).