EFFICIENT LOADING OF HLA-DR WITH A T-HELPER EPITOPE BY GENETIC EXCHANGE OF CLIP

The HLA class II-associated invariant chain (Ii)-derived peptide (CLIP ) occupies the peptide binding groove during assembly in the endoplasm ic reticulum, travels with HLA class II to endosomal compartments, and is subsequently released to allow binding of antigenic peptides. We i nvestigated whether the exchange of CLIP with a known T helper epitope at the DNA level would lead to efficient loading of this helper epito pe onto HLA class II. For this purpose, a versatile Ii-encoding expres sion vector was created in which CLIP can be replaced with a helper ep itope of choice. Upon supertransfection of HLA-DR1-transfected 293 cel ls with an Ii vector encoding a known T helper epitope (HA307-319), pr edominantly length variants of this epitope were detected in associati on with the HLA-DR1 molecules of these cells. Moreover, this transfect ant was efficiently recognized by a peptide-specific T helper clone (H A1.7). The results suggest that this type of Ii vector can be used to create potent class II+ cellular vaccines in which defined T cell epit opes are continuously synthesized.