HLA-DR peptide-induced alloreactive T cell lines reveal an HLA-DR sequence that can be both "dominant" and "cryptic":...

Previously, we reported on a T cell line, ThoU6, which we obtained through stimulation of DPw3+ cells with a synthetic "DR3 peptide" with a sequence identical to the third hypervariable region of the DRB1*0301 chain. This T cell line recognizes both the synthetic peptide presented by DPw3 as well as DR3+ DPw3+ stimulator cells. This implies that the synthetic DR3 peptide has a natural counterpart in DR3-positive cells. Here we describe the recognition pattern of another T cell line that was sensitized with the same synthetic DR3 peptide. This T cell line, BieU6, shows both HLA-DRw13/Dw18 (self)-restricted recognition of the synthetic DR3 peptide and allorecognition towards DR13/Dw19, a molecule which is highly homologous to Dw18, in the absence of synthetic peptide. These results suggest that the epitope formed by the Dw18 molecule plus the synthetic DR3 peptide and recognized by T cell line BieU6 mimics the Dw19 molecule. The potential role for a Dw19-specific peptide is discussed. The inability of T cell line BieU6 to recognize Dw18+ DR3+ cells indicates that, in this case, the synthetic DR3 peptide is "cryptic", i.e. does not have a natural counterpart that is effectively presented to T cells. Mapping of the shortest peptides recognized by T cell lines ThoU6 and BieU6 indicate that these sequences are fully overlapping. We, therefore, suggest that the antigen-presenting molecules, HLA-DPw3 and HLA-Dw18, differ in their accessibility for self peptides derived from the third hypervariable region of DR molecules. These observations may be explained by allele-specific processing.