E2 is a 32 kd human T-cell surface glycoprotein involved in spontaneous rosette formation with erythrocytes. A 1.11 kb cDNA was isolated from a lambda gt11 expression library by screening with monoclonal antibodies directed against E2. The primary structure of E2, deduced from the nucleotide sequence of its gene, comprises 185 amino acids and is devoid of N-linked glycosylation sites. The E2 protein is rich in proline residues and displays an organization typical of an integral membrane protein. Northern blotting showed a good correlation between mRNA abundance, E2 surface density and the level of T cell differentiation. In fact, nucleotide sequencing revealed that E2 is the MIC2 gene product, previously identified with the 12E7 Mab. Xg(a-) female individuals have no E2 molecule on the surface of their red cells, in contrast with Xg(a+) individuals, but have the molecule in their cytoplasm, in the form of the 28 kd precursor. These findings show that the E2 antigen, a cell surface molecule involved in T cell adhesion processes, is the product of the MIC2 gene, the only pseudoautosomal gene to be described in man.