Antigen-specific T cells with monogamous or promiscuous restriction patterns are sensitive to different HLA-DR beta chain substitutions

The contributions of the amino acids at 13 polymorphic positions in the HLA-DR7 beta 1 chain to T cell recognition of two antigenic peptides of tetanus toxin (p2 and p30) were assessed using transfectants expressing mutant DR7 beta 1 chains as APC for six toxin-specific T cell clones with two different restriction patterns: monogamous (restricted by DR7 only) or promiscuous (restricted by DR7; DR1; DR2, Dw21; and DR4, Dw4). Each of the 13 substitutions significantly decreased or eliminated the ability of the DR7 molecule to present a peptide to one or more of the T cell clones, but none of the substitutions abolished recognition by all clones. Interestingly, substitutions at positions 4 and 25, which are predicted in the class II model to be located outside the peptide binding groove, decreased the ability of the DR7 molecule to present Ag to some clones but not to others. Each of the four clones specific for the p2 peptide and the two clones specific for peptide p30 had a different reactivity pattern to the panel of DR7 beta 1 mutants, indicating that the TCR of each clone has a different view of the p2/DR7 or p30/DR7 complex. These data emphasize the complexity of the interactions of multiple residues in DR7 beta 1 chains in Ag-specific T cell recognition.