Fig. 5: Structural basis for Para.09 affinity gain to TREM2. | Nature Communications

Fig. 5: Structural basis for Para.09 affinity gain to TREM2.

From: Rapid affinity optimization of an anti-TREM2 clinical lead antibody by cross-lineage immune repertoire mining

Fig. 5

a Alignment of 3.10C2 and Para.09 within the CDR. Direct TREM2 interactions shared between hu3.10C2 and huPara.09 are listed on the bottom row. Interactions that are exclusive to huPara.09 are highlighted in red. Framework 4 region (FR4) differences are due to differences in JH segment use in clones 3.10C2 and Para.09, shown in Supplementary Fig. 3. IMGT® numbering shown. b Close up view of mutation of G106h in hu3.10C2 (white) to D106h in huPara.09 (green) allows for additional hydrogen bond (black dashes) to the TREM2 peptide (dark salmon). c Structural consequence on CDR-H3 of Para.09 I107h introduction (green) compared hu3.10C2 (white). d Comparison of TREM2 H154 binding pocket in hu3.10C2 (left) and huPara.09 (right). The VH (green) and VL (cyan) of both fabs are shown in surface representation and the TREM2 peptide is shown in dark salmon ribbon. The key TREM2 H154 residue being buried is shown in sticks. The key L107h/L115h residue is highlighted in red. e Close up view of huPara.09 E116h (green) compared to hu3.10C2 D116h (white). Both residues maintain hydrogen bond interactions with TREM2 S160 (black and yellow dashes). H1, H2 and H3 indicate residues in CDR H1, H2 and H3 regions.

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