Structural basis of chronic beryllium disease: linking allergic hypersensitivity and autoimmunity.
Cell
; 158(1): 132-42, 2014 Jul 03.
Article
in En
| MEDLINE
| ID: mdl-24995984
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Berylliosis
/
Beryllium
/
Receptors, Antigen, T-Cell
/
CD4-Positive T-Lymphocytes
/
Autoimmunity
/
HLA-DP beta-Chains
/
Hypersensitivity
Limits:
Humans
Language:
En
Journal:
Cell
Year:
2014
Document type:
Article
Affiliation country: