Intracellular protein modification associated with altered T cell functions in autoimmunity.
J Immunol
; 177(7): 4541-9, 2006 Oct 01.
Article
in En
| MEDLINE
| ID: mdl-16982891
ABSTRACT
Posttranslational protein modifications influence a number of immunologic responses ranging from intracellular signaling to protein processing and presentation. One such modification, termed isoaspartyl (isoAsp), is the spontaneous nonenzymatic modification of aspartic acid residues occurring at physiologic pH and temperature. In this study, we have examined the intracellular levels of isoAsp residues in self-proteins from MRL(+/+), MRL/lpr, and NZB/W F(1) mouse strains compared with nonautoimmune B10.BR mice. In contrast to control B10.BR or NZB/W mice, the isoAsp content in MRL autoimmune mice increased and accumulated with age in erythrocytes, brain, kidney, and T lymphocytes. Moreover, T cells that hyperproliferate to antigenic stimulation in MRL mice also have elevated intracellular isoAsp protein content. Protein l-isoaspartate O-methyltransferase activity, a repair enzyme for isoAsp residues in vivo, remains stable with age in all strains of mice. These studies demonstrate a role for the accumulation of intracellular isoAsp proteins associated with T cell proliferative defects of MRL autoimmune mice.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
T-Lymphocytes
/
Autoimmunity
/
Protein Processing, Post-Translational
/
Aspartic Acid
/
Lupus Erythematosus, Systemic
Type of study:
Risk_factors_studies
Limits:
Animals
Language:
En
Journal:
J Immunol
Year:
2006
Document type:
Article