Direct binding of autoimmune disease related T cell epitopes to purified Lewis rat MHC class II molecules

TY - JOUR

T1 - Direct binding of autoimmune disease related T cell epitopes to purified Lewis rat MHC class II molecules

AU - Joosten, I

AU - Wauben, M H

AU - Holewijn, M C

AU - Reske, K

AU - Pedersen, L O

AU - Roosenboom, C F

AU - Hensen, E J

AU - van Eden, W

AU - Buus, S

N1 - Keywords: Amino Acid Sequence; Animals; Autoantigens; Autoimmune Diseases; Binding, Competitive; Cattle; Cell Line; Cells, Cultured; Chemiluminescent Measurements; Epitopes; Histocompatibility Antigens Class II; Molecular Sequence Data; Peptides; Rats; Rats, Inbred Lew; Sensitivity and Specificity; T-Lymphocytes

PY - 1994

Y1 - 1994

N2 - New strategies applied in the treatment of experimental autoimmune disease models involve blocking or modulation of MHC-peptide-TCR interactions either at the level of peptide-MHC interaction or, alternatively, at the level of T cell recognition. In order to identify useful competitor peptides one must be able to assess peptide-MHC interactions. Several well described autoimmune disease models exist in the Lewis rat and thus this particular rat strain provides a good model system to study the effect of competitor peptides. So far no information has been available on the peptide binding characteristics of the Lewis rat MHC class II RT1.B1 molecule. We have now developed a biochemical binding assay which enables competition studies in which the relative MHC binding affinity of a set of non-labelled peptides can be assessed while employing detection of biotinylated marker peptides by chemiluminescence. The assay is sensitive and specific. We have used this assay to determine the binding characteristics of several disease associated T cell determinants and their sequence analogues in the Lewis rat. Notably, most of the autoimmune disease associated peptide sequences tested were found to be intermediate to poor binders. Single amino acid substitutions at defined positions were sufficient to turn certain peptides into good binders. These results are relevant to the design of competitor peptides in the treatment of experimental autoimmune diseases.

AB - New strategies applied in the treatment of experimental autoimmune disease models involve blocking or modulation of MHC-peptide-TCR interactions either at the level of peptide-MHC interaction or, alternatively, at the level of T cell recognition. In order to identify useful competitor peptides one must be able to assess peptide-MHC interactions. Several well described autoimmune disease models exist in the Lewis rat and thus this particular rat strain provides a good model system to study the effect of competitor peptides. So far no information has been available on the peptide binding characteristics of the Lewis rat MHC class II RT1.B1 molecule. We have now developed a biochemical binding assay which enables competition studies in which the relative MHC binding affinity of a set of non-labelled peptides can be assessed while employing detection of biotinylated marker peptides by chemiluminescence. The assay is sensitive and specific. We have used this assay to determine the binding characteristics of several disease associated T cell determinants and their sequence analogues in the Lewis rat. Notably, most of the autoimmune disease associated peptide sequences tested were found to be intermediate to poor binders. Single amino acid substitutions at defined positions were sufficient to turn certain peptides into good binders. These results are relevant to the design of competitor peptides in the treatment of experimental autoimmune diseases.

M3 - Journal article

C2 - 7521668

SN - 0953-8178

VL - 6

SP - 751

EP - 759

JO - International Immunology

JF - International Immunology

IS - 5

ER -