Structural highlights
Function
[HA11_MOUSE] Involved in the presentation of foreign antigens to the immune system. [GLYC_LYCVW] The stable signal peptide (SSP) is cleaved and functions as a signal peptide. In addition, it is apparently retained as the third component of the GP complex. The SSP is required for efficient glycoprotein expression, post-translational maturation cleavage of GP1 and GP2, glycoprotein transport to the cell surface plasma membrane, formation of infectious virus particles, and acid pH-dependent glycoprotein-mediated cell fusion (By similarity). Glycoprotein G1 mediates virus attachment to host receptor alpha-dystroglycan DAG1. This attachment induces virion internalization predominantly through clathrin- and caveolin-independent endocytosis (By similarity). Glycoprotein G2 is a viral fusion protein. Membrane fusion is mediated by conformational changes induced upon acidification in the endosome (Potential). [B2MG_MOUSE] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system.
Publication Abstract from PubMed
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.
Unexpected T-cell recognition of an altered peptide ligand is driven by reversed thermodynamics.,Allerbring EB, Duru AD, Uchtenhagen H, Madhurantakam C, Tomek MB, Grimm S, Mazumdar PA, Friemann R, Uhlin M, Sandalova T, Nygren PA, Achour A Eur J Immunol. 2012 Nov;42(11):2990-3000. doi: 10.1002/eji.201242588. Epub 2012, Sep 20. PMID:22837158[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Allerbring EB, Duru AD, Uchtenhagen H, Madhurantakam C, Tomek MB, Grimm S, Mazumdar PA, Friemann R, Uhlin M, Sandalova T, Nygren PA, Achour A. Unexpected T-cell recognition of an altered peptide ligand is driven by reversed thermodynamics. Eur J Immunol. 2012 Nov;42(11):2990-3000. doi: 10.1002/eji.201242588. Epub 2012, Sep 20. PMID:22837158 doi:http://dx.doi.org/10.1002/eji.201242588
