Cross-restriction of a T cell clone to HLA-DR alleles associated with rheumatoid arthritis: clues to arthritogenic peptide motifs.
OBJECTIVE
To identify distinctive sequence motifs required for productive peptide presentation by those HLA-DR alleles/DR4 subtypes that predispose to rheumatoid arthritis (RA).


METHODS
We tested 10 different HLA-DR4 subtypes for presentation of acetylcholine receptor peptides to 8 different DR4-restricted T cell lines/clones in proliferation assays.


RESULTS
Seven of the 8 T cells depended absolutely on either the autologous Lys71 (in Dw4) or Arg71 (e.g., Dw14), despite these alleles' similar charge and RA associations. In contrast, the PM-A T cell was only mildly affected by this interchange. Moreover, after minor modifications, peptides were presented to this unusual T cell preferentially by all the RA-associated subtypes of DR4 as well as by 2 other DR alleles (DR1 and DR1402) that predispose to RA.


CONCLUSIONS
This coincident cross-restriction to all the RA-associated HLA-DR alleles except DR10 shows that there could even be a single arthritogenic peptide; we now suggest a possible consensus motif.
D000483:Alleles; D000938:Antigen-Presenting Cells; D001120:Arginine / Q000235:genetics; D001172:Arthritis, Rheumatoid / Q000473:pathology*; D002999:Clone Cells / Q000276:immunology*; D003429:Cross Reactions; D005998:Glycine / Q000235:genetics; D006684:HLA-DR Antigens / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008239:Lysine / Q000235:genetics; D017354:Point Mutation; D011487:Protein Conformation; D013601:T-Lymphocytes / Q000166:cytology*; D014364:Tryptophan / Q000235:genetics