MHC class II-bound self peptides from autoimmune MRL/lpr mice reveal potential T cell epitopes for autoantibody production in murine systemic lupus erythematosus.
The systemic lupus erythematosus-like syndrome in MRL/lpr mice involves high-titered IgG autoantibodies, particularly antinuclear Abs that target histones, DNA, and RNA particles. Although T cell help is required for the generation of antinuclear Abs, the epitopes recognized by such helper T cells are unknown. To address this question, we isolated and sequenced self peptides bound by MHC class II molecules from MRL/lpr mice. We identified a number of peptides that are not seen in similar preparations from nonautoimmune C3H animals. The "abnormal" peptide donors include histone, a protein component of a small nuclear ribonucleoprotein, ribosomal proteins, and RNA processing enzymes. We postulate that the peptides from these donors are T cell epitopes required for the generation of the most frequent antinuclear Abs specificities seen in MRL/lpr mice.
Freed
J H
JH
Division of Basic Immunology, Department of Medicine, National Jewish Medical and Research Center, Denver, CO 80206, USA. freedj@njc.org
Marrs
A
A
VanderWall
J
J
Cohen
P L
PL
Eisenberg
R A
RA
D020816:Amino Acid Motifs / Q000276:immunology; D000595:Amino Acid Sequence; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis*; D001324:Autoantigens / Q000276:immunology / Q000378:metabolism*; D018984:Epitopes, T-Lymphocyte / Q000302:isolation & purification / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000302:isolation & purification / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000378:metabolism; D008198:Lymph Nodes / Q000737:chemistry / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D019463:Mice, Inbred MRL lpr; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism*; D011485:Protein Binding / Q000276:immunology; D017386:Sequence Homology, Amino Acid
D001323:Autoantibodies; D001324:Autoantigens; D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D010446:Peptide Fragments