Crystal structure of an anti-interleukin-2 monoclonal antibody Fab complexed with an antigenic nonapeptide

The three-dimensional structure of the Fab fragment of a monoclonal antibod y (LNKB-2) to human interleukin-2 (IL-2) complexed with a synthetic antigen ic nonapeptide, Ac-Lys-Pro-Leu-Glu-Glu-Vnl-Leu-Asn-Leu-OMe, has been determ ined at 3.0 Angstrom resolution. In the structure, four out of the six hype rvariable loops of the Fab (complementarity determining regions [CDRs] L1, H1, H2, and H3) Ie involved in peptide association through hydrogen bonding , salt bridge formation, and hydrophobic interactions. The Tyr residues in the Fab antigen binding site play a major role in antigen-antibody recognit ion. The are structures of the complexed and uncomplexed Fab were compared. Ln the antigen binding site the CDR-L1 loop of the antibody shows the larg est structural changes upon peptide binding. The peptide adopts a mostly al pha -helical conformation similar to that in the epitope fragment 64-72 of the IL-2 antigen. The side chains of residues Leu 66, Val 69, and Leu 70, w hich are shielded internally in the IL-2 structure, are involved in interac tions with the Fab in the complex studied. This indicates that antibody-ant igen complexation involves a significant rearrangement of the epitope-conta ining region of the IL-2 with retention of the alpha -helical character of the epitope fragment.