Intracellular protein modification associated with altered T cell functions in autoimmunity.

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.

9 Figures and Tables

Statistics

05010015020072008200920102011201220132014201520162017
Citations per Year

234 Citations

Semantic Scholar estimates that this publication has 234 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{Yang2006IntracellularPM, title={Intracellular protein modification associated with altered T cell functions in autoimmunity.}, author={Mei-Ling Yang and Hester A. Doyle and Renelle J. Gee and Jonathan D. Lowenson and Steven G. Clarke and Brian R. Lawson and Dana W Aswad and Mark J. Mamula}, journal={Journal of immunology}, year={2006}, volume={177 7}, pages={4541-9} }