Cytotoxic T lymphocytes discriminate between isomeric forms of the same hapten

We have analysed the ability of fluorescein-specific cytolytic T lymphocytes (CTLs) to lyse a variety of hapten-derived target cells. Our data demonstrate that: (i) fluorescein-specific CTLs distinguish between target cells conjugated with isomeric forms of the hapten in a way that is not attributable to differences in the target cell density of the two hapten isomers; (ii) the relative orientation of the haptenic moiety with respect to the target cell membrane is more important than the chemical nature of the hapten/protein linkage. We interpret these data as supporting a model of the T-cell receptor in which the elements that recognize the extrinsic and the restricting Class 1 major histocompatibility complex (MHC) antigens are sterically constrained and unable to rotate independently of one another.