Intramolecular T cell spreading in unprimed MRL/lpr mice: Importance of the U1-70k protein sequence 131–151

✍ Scribed by Fanny Monneaux; Véronique Parietti; Jean-Paul Briand; Sylviane Muller

• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: English
• Weight: 222 KB
• Volume: 50
• Category: Article
• ISSN: 0004-3591
• DOI: 10.1002/art.20510

✦ Synopsis

Abstract

Objective

To analyze spontaneous T cell spreading against determinants of the U1‐70K protein in young autoimmune MRL/lpr lupus mice, in comparison with the T cell spreading occurring in normal BALB/c mice immunized with peptide 131–151 of this protein.

Methods

Peripheral blood lymphocytes (PBLs) from both unprimed MRL/lpr mice and immunized BALB/c mice were tested for their ability to proliferate ex vivo in response to 18 overlapping peptides of the U1‐70K spliceosomal protein, using assays for lymphocyte proliferation and secretion of interleukin‐2.

Results

The proliferative response to peptides of the U1‐70K protein evolved rapidly in MRL/lpr mice tested at different ages. At least 5 peptides were recognized by PBLs from 8‐week‐old autoimmune mice, whereas a different peptide was recognized by PBLs from MRL/lpr mice at 12 weeks of age. At 15 weeks, the proliferative response was weak or negative when assessed with any of the test peptides. At least 2 major peptides recognized by MRL/lpr PBLs were also recognized by PBLs generated in the BALB/c mice primed with peptide 131–151. We further demonstrated that, in preautoimmune MRL/lpr mice, repeated administration of phosphorylated peptide 131–151 (called P140), which was shown previously to be protective, transiently abolished T cell intramolecular spreading to other regions of the 70K protein.

Conclusion

This is the first study to demonstrate that intramolecular T cell spreading effectively occurs in MRL/lpr mice with lupus, and that region 131–151 is important in the cascade of events observed in the murine lupus response. This sequence might originate a mechanism of tolerance spreading that leads to the beneficial effect observed in MRL/lpr mice after treatment with the phosphorylated peptide 131–151.