Human T lymphocytes that express the T4 (CD4) cell-surface antigen play a central role in the regulation of immune responses . T4+ lymphocytes are, however, a functionally heterogeneous population of cells that can be subdivided by the mAb anti-2H4, into the T4', 2H4+ subset that induces suppressor activity of the T8+ suppressor T cells, and the T4+, 2H4T cell subset with helper function (1). Biochemical analysis has shown that the 2H4 antigens are members of a family of high molecular weight cell surface glycoproteins known as leukocyte common antigens (LCAs), T200 or CD45 (2). While some anti-LCA mAbs react with all forms of LCAs, which are resolved into four or more proteins by SDSPAGE, other anti-LCA mAbs, including anti-2H4, react only with a subset of these proteins (2-4) . In functional studies, anti-2H4, but not anti-LCA mAbs that are reactive with all LCA members, has been shown to block the induction of suppression by T4+, 2H4' cells (5). These studies suggest that the 2H4 epitope may be directly involved in the induction of suppressor function . It is, therefore, important to establish the molecular basis of the 2H4 epitope expression to understand the function of the suppressor-inducer T cell subset . Recently, it was demonstrated (6, 7) that the genetic basis of the heterogeneity of the human LCAs is the differential usage of three exons of the single LCA gene. The exons termed A, B, and C, which are differentially used, encode 66, 47, and 48 amino acids, respectively, of the amino-proximal end of the LCA molecules (6). In a previous report (6), cDNA clones corresponding to three LCA structures were isolated, and the existence of at least two more forms of LCA mRNA was shown by Northern hybridization experiments. Since then, we have isolated a cDNA clone that corresponds to one of the predicted structures . In this communication, we study the molecular basis of the 2H4 epitope expression using these cDNA clones encoding four of the LCAs.