4P5K

Structural Basis of Chronic Beryllium Disease: Bridging the Gap Between Allergy and Autoimmunity

Summary for 4P5K

• Entry DOI: 10.2210/pdb4p5k/pdb
• Related: 4P4K 4P4R 4P57
• Descriptor: HLA class II histocompatibility antigen, DP alpha 1 chain, RAS peptide,HLA class II histocompatibility antigen, DP beta 1 chain (2 entities in total)
• Functional Keywords: mhc, tcr, complex, hla, chronic beryllium disease, allergy, autoimmunity, immune system
• Biological source: Homo sapiens (Human); More
• Cellular location: Cell membrane; Single-pass type I membrane protein: P20036
• Total number of polymer chains: 4
• Total formula weight: 91181.49

Authors

Clayton, G.M.,Wang, Y.,Crawford, F.,Novikov, A.,Wimberly, B.T.,Kieft, J.S.,Falta, M.T.,Bowerman, N.A.,Marrack, P.,Fontenot, A.P.,Dai, S.,Kappler, J.W. (deposition date: 2014-03-17, release date: 2015-01-21, Last modification date: 2024-10-09)

Primary citation

Clayton, G.M.,Wang, Y.,Crawford, F.,Novikov, A.,Wimberly, B.T.,Kieft, J.S.,Falta, M.T.,Bowerman, N.A.,Marrack, P.,Fontenot, A.P.,Dai, S.,Kappler, J.W.
Structural basis of chronic beryllium disease: linking allergic hypersensitivity and autoimmunity.
Cell, 158:132-142, 2014

PubMed Abstract: T-cell-mediated hypersensitivity to metal cations is common in humans. How the T cell antigen receptor (TCR) recognizes these cations bound to a major histocompatibility complex (MHC) protein and self-peptide is unknown. Individuals carrying the MHCII allele, HLA-DP2, are at risk for chronic beryllium disease (CBD), a debilitating inflammatory lung condition caused by the reaction of CD4 T cells to inhaled beryllium. Here, we show that the T cell ligand is created when a Be(2+) cation becomes buried in an HLA-DP2/peptide complex, where it is coordinated by both MHC and peptide acidic amino acids. Surprisingly, the TCR does not interact with the Be(2+) itself, but rather with surface changes induced by the firmly bound Be(2+) and an accompanying Na(+) cation. Thus, CBD, by creating a new antigen by indirectly modifying the structure of preexisting self MHC-peptide complex, lies on the border between allergic hypersensitivity and autoimmunity.

PubMed: 24995984
DOI: 10.1016/j.cell.2014.04.048

Experimental method

X-RAY DIFFRACTION (2.59 Å)