Cell surface expression and metabolism of major histocompatibility complexclass II invariant chain (CD74) by diverse cell lines

We previously described the processing of antibodies to CD74 (the major his tocompatibility complex Class II-associated invariant chain, Ii), by B-cell lymphoma cell lines. These cells expressed relatively low levels of Ii on the surface, but the molecules were rapidly internalized and replaced by ne w molecules, so that approximate to 8 x 10(6) antibody molecules per cell w ere taken up per day. We herein report the results of similar studies with other cell types, namely a melanoma, a colon carcinoma, a T-cell lymphoma a nd B-lymphoblastoid cell lines. The melanoma and the carcinoma were treated with interferon-gamma to induce high levels of the antigen. The T-cell lym phoma, HUT 78, was selected specifically because it was previously reported to lack cell surface Ii, while expressing the molecule intracellularly. Ho wever, HUT 78 displayed Ii on the cell surface, as did the other cell lines tested, and catabolism of the antibody was very fast on all of the cell li nes. The capacity of four of the cell lines for cumulative antibody uptake was evaluated, using 'residualizing' radiolabels, which are trapped within the cell after catabolism of the antibody to which they were conjugated. A high level of uptake was observed in all cases, although there was signific ant variation between the cell lines. With melanoma SK-MEL-37, the total LL 1 uptake in 24 hr was nearly 10(7) molecules per cell and the average turno ver time for Ii on the cell surface was 4 min; with carcinoma HT-29, the to tal LL1 uptake in 24 hr was approximate to 10(6) molecules per cell, and th e average turnover time for Ii on the cell surface was 27 min. Based on the cell content of mature class II antigens (alpha beta), these data suggest that a large fraction, or all, of immature class II molecules (alpha beta I i) reach the cell surface before entering the peptide-loading compartment, independent of the particular cell type.