A cytotoxic human hybridoma monoclonal antibody (TrJ6) defining an epitope expressed by HLA-DQ4 and -DQ5.

We have generated a cytotoxic human hybridoma monoclonal IgM lambda antibody, designated TrJ6, that is specific for a new epitope shared by HLA-DQ4 and -DQ5. TrJ6 strongly killed all ten DQ4-bearing cells and weakly killed all four DQ5-bearing cell lines. In contrast, none of the 36 cell lines lacking DQ4 and DQ5 antigens was recognized by TrJ6. This was confirmed by fluorescence cytometry. The specific binding of TrJ6 to a DQ4-bearing line was efficiently blocked by IIB3 (murine anti-DQ8+9+4+5+6 mAb) and TrG6 (human IgG mAb against DQ4+5+6), confirming that TrJ6 is specific for a polymorphic DQ epitope. TrJ6 can be used to distinguish DQ5+ from DQ6+ B-lymphoblastoid cells. DQ4 beta and DQ5 beta chains share one unique residue (Ser-74) and one relatively unique residue (Val-75), which may therefore need to be coexpressed in order for the TrJ6 epitope to be formed. Alternatively, Ser-74 alone contributes critically to the allospecificity of this epitope. 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 the TrJ6 epitope because TrJ6 reacted stronger with DQ4- than with DQ5-bearing cell lines.