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

Arthritis Rheum. 2004 Oct;50(10):3232-8. doi: 10.1002/art.20510.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Division / immunology
  • Female
  • Immunization
  • Lupus Erythematosus, Systemic / immunology*
  • Lymphocytes / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred MRL lpr
  • Peptides / physiology
  • Phosphorylation
  • Ribonucleoprotein, U1 Small Nuclear / immunology
  • Ribonucleoprotein, U1 Small Nuclear / physiology*


  • Peptides
  • Ribonucleoprotein, U1 Small Nuclear
  • SNRNP70 protein, human