THE E2 MOLECULE (CD99) SPECIFICALLY TRIGGERS HOMOTYPIC AGGREGATION OFCD4(+) CD8(+) THYMOCYTES

We have previously described E2 as a 32-kDa transmembrane glycoprotein displaying an isomorphism, as two epitopes (defined by mAbs O662 and L129) are widely d istributed on T cells whereas two epitopes are rest ricted to T cell subsets (defined by mAbs D44 and 12E7). E2, the MIC-2 gene product, is involved in T cell adhesion because anti-E2 mAbs aga inst pan T epitopes block spontaneous T cell rosettes. Pan T E2 mAbs a re also able to induce exposure of the phosphatidylserine at the thymo cyte surface but not at the su rface of mature T lymphocytes, an event most likely linked to adhesion phenomena. We now show here that the a nti-E2 mAbs (O662 and L129) that block rosettes and induce phosphatidy lserine exposure at the thymocyte surface, and not those reacting with epitopes not involved in adhesion, also trigger aggregation of certai n immature T cell lines and no other cell lines tested. Among the norm al cells tested, anti-E2 mAbs exclusively induce homotypic aggregation of CD4(+) CD8(+) human thymocytes. This phenomenon is temperature, en ergy, and Mg++ dependent, and requires an intact cytoskeleton. These a dhesion properties are rather characteristic of integrins. Nevertheles s, mAb against beta 1, beta 2, and beta 3 integrin chains, as well as those against alpha-chains known to be present on thymocytes, are unab le to block corticothymocyte aggregation. We conclude that E2 triggers on corticothymocytes and no other T cells a homotypic adhesion pathwa y most likely mediated by an uncharacterized integrin.