3QUL

Crystal structures of the murine class I major histocompatibility complex H-2Db in complex with LCMV-derived gp33 altered peptide ligand (Y4S)

Summary for 3QUL

• Entry DOI: 10.2210/pdb3qul/pdb
• Related: 1S7U 1S7V 1S7W 1S7X 3QUK
• Descriptor: H-2 class I histocompatibility antigen, D-B alpha chain, Beta-2-microglobulin, Pre-glycoprotein polyprotein GP complex, ... (4 entities in total)
• Functional Keywords: murine mhc, lcmv, receptor binding, beta2-microglobulin, immune system, t cell recognition, t cell receptor, cell surface
• Biological source: Mus musculus (Mouse); More
• Cellular location: Membrane; Single-pass type I membrane protein: P01899; Secreted: P01887; Glycoprotein G1: Virion membrane ; Peripheral membrane protein . Glycoprotein G2: Virion membrane ; Single-pass membrane protein . Stable signal peptide: Virion membrane ; Multi-pass membrane protein : P07399
• Total number of polymer chains: 12
• Total formula weight: 179044.79

Authors

Allerbring, E.,Duru, A.D.,Uchtenhagen, H.,Madhurantakam, C.,Grimm, S.,Tomek, M.B.,Mazumdar, P.A.,Spetz, A.,Friemann, R.,Sandalova, T.,Uhlin, M.,Nygren, P.,Achour, A. (deposition date: 2011-02-24, release date: 2012-03-21, Last modification date: 2023-09-13)

Primary citation

Allerbring, E.B.,Duru, A.D.,Uchtenhagen, H.,Madhurantakam, C.,Tomek, M.B.,Grimm, S.,Mazumdar, P.A.,Friemann, R.,Uhlin, M.,Sandalova, T.,Nygren, P.A.,Achour, A.
Unexpected T-cell recognition of an altered peptide ligand is driven by reversed thermodynamics.
Eur.J.Immunol., 42:2990-3000, 2012

PubMed Abstract: The molecular basis underlying T-cell recognition of MHC molecules presenting altered peptide ligands is still not well-established. A hierarchy of T-cell activation by MHC class I-restricted altered peptide ligands has been defined using the T-cell receptor P14 specific for H-2D(b) in complex with the immunodominant lymphocytic choriomeningitis virus peptide gp33 (KAVYNFATM). While substitution of tyrosine to phenylalanine (Y4F) or serine (Y4S) abolished recognition by P14, the TCR unexpectedly recognized H-2D(b) in complex with the alanine-substituted semiagonist Y4A, which displayed the most significant structural modification. The observed functional hierarchy gp33 > Y4A > Y4S = Y4F was neither due to higher stabilization capacity nor to differences in structural conformation. However, thermodynamic analysis demonstrated that while recognition of the full agonist H-2D(b) /gp33 was strictly enthalpy driven, recognition of the weak agonist H-2D(b) /Y4A was instead entropy driven with a large reduction in the favorable enthalpy term. The fourfold larger negative heat capacity derived for the interaction of P14 with H-2D(b) /gp33 compared with H-2D(b) /Y4A can possibly be explained by higher water entrapment at the TCR/MHC interface, which is also consistent with the measured opposite entropy contributions for the interactions of P14 with both MHCs. In conclusion, this study demonstrates that P14 makes use of different strategies to adapt to structural modifications in the MHC/peptide complex.

PubMed: 22837158
DOI: 10.1002/eji.201242588

Experimental method

X-RAY DIFFRACTION (2 Å)