Mutagenesis of beryllium-specific TCRs suggests an unusual binding topology for antigen recognition.

ABSTRACT: Unconventional Ags, such as metals, stimulate T cells in a very specific manner. To delineate the binding landscape for metal-specific T cell recognition, alanine screens were performed on a set of Be-specific TCRs derived from the lung of a chronic beryllium disease patient. These TCRs are HLA-DP2-restricted and express nearly identical TCR V?5.1 chains coupled with different TCR ?-chains. Site-specific mutagenesis of all amino acids comprising the CDRs of the TCRA and TCRB genes showed a dominant role for V?5.1 residues in Be recognition, with little contribution from the TCR ?-chain. Solvent-exposed residues along the ?-helices of the HLA-DP2 ?- and ?-chains were also mutated to alanine. Two ?-chain residues, located near the proposed Be binding site of HLA-DP2, played a dominant role in T cell recognition with no contribution from the HLA-DP2 ?-chain. These findings suggest that Be-specific T cells recognize Ag using an unconventional binding topology, with the majority of interactions contributed by TCR V?5.1 residues and the HLA-DP2 ?1-chain. Thus, unusual docking topologies are not exclusively used by autoreactive T cells, but also for the recognition of unconventional metal Ags, such as Be.

SUBMITTER: Bowerman NA 

PROVIDER: S-EPMC3178675 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature