Membrane-bound H-2 and H-Y antigens move independently of each other

ON exposure to foreign antigens, mouse T lymphocytes can be stimulated to mature into cytotoxic cells able to kill target cells carrying these antigens^1-4. Killing is restricted to cells bearing, in addition to the foreign antigen, the same H-2K or H-2D antigens as the stimulating cell. Cells bearing different H-2 antigens are not killed. To kill a lymphocyte, two recognition steps are necessary: one involving the foreign antigen and another involving H-2 antigens. This associative recognition has been demonstrated for many antigens and must be considered a general phenomenon. Two opposing views have been proposed to explain the associative recognition⁵. According to the altered-self hypothesis, the antigen links up on the cell membrane with H-2 molecules and the complex of antigen plus H-2 is then recognised by a single receptor on a T lymphocyte. According to the dual recognition hypothesis, each T lymphocyte has two receptors, one for the antigen and the other for H-2, and it is the combination of the two receptors on each cell that is responsible for the associative recognition. The strongest evidence in favour of the first hypothesis is the report of a physical association between antigens and H-2 (see, for example, ref. 6). The link-up of the antigen to H-2, however, might not be related directly to the associative recognition, but rather reflect some other phenomenon in the membrane, in which case there should be examples of associative recognition without a linkage between the antigens. We present evidence for such an association.