[The spliceosome and its interest for lupus therapy].
BACKGROUND
The spliceosome, which is a particle containing a molecule of U-RNA and proteins that are specific to each U ribonuclear particle (U-snRNP) or common to every U-snRNPs, is one of the numerous nuclear targets recognized by the antibodies (Abs) and CD4+ T cells from patients with systemic lupus erythematosus and lupus mice.


METHODS
We recently characterized a peptide from the spliceosomal protein U1-70K (sequence 131-151), which is recognized by the Abs and CD4+ T cells from lupus mice and patients. This peptide contains a conserved RNP1 motif, which is also present in other spliceosomal proteins targeted by the Abs from individuals with lupus. We further showed that peptide 131-151 containing a phosphoserine at position 140 (peptide P140) possessed tolerogenic properties in lupus mice and was recognized by the Abs and CD4+ T cells from lupus patients.


CONCLUSIONS
Thanks to its RNP1 motif, the peptide P140 might play an important role in the initiation and perpetuation steps of the humoral and cellular immune response diversification in lupus individuals. Therapeutic and particularly immunomodulating properties of P140 peptide are being evaluated in humans (a phase III clinical trial will be undertaken in the next weeks).
Monneaux
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F
CNRS UPR9021, immunologie et chimie thérapeutiques, institut de biologie moléculaire et cellulaire, 15 rue René-Descartes, 67000 Strasbourg, France.
Muller
S
S
D020816:Amino Acid Motifs; D000818:Animals; D000906:Antibodies / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D017124:Conserved Sequence; D004274:DNA, Recombinant; D000939:Epitopes; D006239:Haplotypes; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000628:therapy; D051379:Mice; D019463:Mice, Inbred MRL lpr; D008814:Mice, Inbred NZB; D010768:Phosphoserine / Q000032:analysis / Q000276:immunology; D017412:Ribonucleoprotein, U1 Small Nuclear / Q000032:analysis / Q000276:immunology; D020539:Sequence Analysis, Protein; D012694:Serine / Q000032:analysis; D017381:Spliceosomes / Q000276:immunology*
D000906:Antibodies; D004274:DNA, Recombinant; D000939:Epitopes; D017412:Ribonucleoprotein, U1 Small Nuclear; C490688:SNRNP70 protein, human; C490687:Snrnp70 protein, mouse; D010768:Phosphoserine; D012694:Serine