AN HLA-DRB ALPHA-HELIX MOTIF SHARED BY DR11 AND DR8 ALLELES IS IMPLICATED IN THE PLURIALLELIC RESTRICTION OF PEPTIDE-SPECIFIC T-CELL LINES

The T-cell recognition of HLA-DR-peptide complexes is generally restri cted by the polymorphism of the DRB molecules but pluriallelic restric tion has been described. The molecular basis of restriction and promis cuity of such peptide-specific responses is poorly understood. We isol ated a panel of T-cell lines specific for the tetanus toxin peptide p2 (TT830-843) exhibiting pluriallelic restriction by DR11 and DR8 allel es. Fine restriction specificity of the T-cell lines was examined in f unctional assays against DR oligotyped APCs expressing different varia nts of DR11 and DR8 alleles. Our results show that (a) polymorphisms b etween serologically related alleles are relevant in terms of restrict ion of the peptide-specific T-cell response; in some instances, a sing le amino acid substitution can determine the restriction of a T-cell l ine; (b) different patterns of restriction are not the result of speci fic differences in DR-p2 binding as p2 peptide binds to all DR11 and D R8 alleles tested (DRB11101, -1102, -1103, -1104, 110X, -0801, -0802, -0803, and -0806); and (c) pluriallelic restriction of the peptide-sp ecific T-cell response correlates with the presence of a DRB1 alpha-he lix motif (67-71-86) shared by some DR11 and DR8 alleles. Possible imp lications of pluriallelic restriction of peptide-specific T-cell respo nse in autoimmune disorders associated with DR11 and DR8 are discussed .