A CYTOTOXIC HUMAN HYBRIDOMA MONOCLONAL-ANTIBODY (TRJ6) DEFINING AN EPITOPE EXPRESSED BY HLA-DQ4 AND HLA-DQ5

We have generated a cytotoxic human hybridoma monoclonal IgM lambda an tibody, designated TrJ6, that is specific for a new epitope shared by HLA-DQ4 and -DQ5. TrJ6 strongly killed all ten DQ4-bearing cells and w eakly killed all four DQ5-bearing cell lines. In contrast, none of the 36 cell lines lacking DQ4 and DQ5 antigens was recognized by TrJ6. Th is was confirmed by fluorescence cytometry. The specific binding of Tr J6 to a DQ4-bearing line was efficiently blocked by IIB3 (murine anti- DQ8 + 3 + 4 + 5 + 6 mAb) and TrG6 (human IgG mAb against DQ4 + 5 + 6), confirming that TrJ6 is specific for a polymorphic DQ epitope. TrJ6 c an be used to distinguish DQ5(+) from DQ6(+) B-lymphoblastoid cells. D Q4 beta and DQ5 beta chains share one unique residue (Ser-74) and one relatively unique residue (Val-75), which may therefore need to be coe xpressed in order for the TrJ6 epitope to be formed. Alternatively, Se r-74 alone contributes critically to the allospecificity of this epito pe. In addition, one or more of three residues unique for DQ4 (Leu-56, Glu-70, and Asp-71 on the DQ4 beta chain) could also contribute to th e TrJ6 epitope because TrJ6 reacted stronger with DQ4- than with DQ5-b earing cell lines.