The role of polymorphic HLA-DRβchain residues in presentation of viral antigens to T cells

Abstract

The relative importance of 11 polymorphic positions in the HLA-DR7β1 chain in T cell recognition of foreign antigens was investigated using transfectants expressing mutant DR7β1 chains as APC for five rabies virus-specific T cell clones. The results indicate that multiple amino acids, located in both the β-strands and α-helix of DR7β1 in the model of a class II molecule, are involved in DR7-restricted T cell recognition of these antigens. Many of the substitutions appeared to reduce the affinity of an antigenic peptide for the mutant DR7 molecules but did not prevent binding. The heterogeneity of responses of the three G-specific T cell clones to presentation of the G11.3 peptide by several of the mutant DR7 molecules indicates that the T cell receptor (TCR) of each these clones requires a different view of the G11.βDR7 complex and raises the possibility that the G11.3 peptide may bind to the DR7 molecule in more than one conformation.