778 Synthesis and Processing of Thymus Leukemia Antigen

The Tla locus, situated ~ 1 cent imorgan from H-2D, specifies a number of antigens called T L (thymus leukemia) 1 that are expressed only on thymocytes at an early stage of their differentiation and on some leukemias (1, 2). This locus, which is thought to comprise a series of linked structural and regulatory genes (3), has several unique features. These cannot be reviewed here, but three points merit special at tention in the context of the present report. First, the T L product or products bear a physico-chemical resemblance to the K and D products o f H-2 and to at least one of the Q a molecules (4-10) specified by Qa genes linked to Tla, including association with/8-2-microglobulin. Thus, T L typifies one family of glycoproteins specified by genes in and near the major, histocompatibil i ty complex. Second, T L is lacking from the prothymocyte and becomes manifest when this precursor cell is induced to become a thymocyte; but T L is no longer expressed on the fully differentiated T lymphocytes that are derived from early thymocytes. (It is generally presumed that T L + thymocytes represent a normal stage of T-cell development , rather than an abortive side branch, but definitive proof is still lacking.) Third, some strains of mice (TLstrains) do not express T L on their thymocytes and yet do so on many of their leukemias, the set of T L antigens expressed on such leukemias being different from the T L set expressed by leukemias and thymocytes of T L + mice. Thus, in these two respects leukemogenesis is often associated with aberrations o f T L expression. For several reasons T L is an attractive model for s tudying the synthesis, regulation, and posttranscriptional elaboration of glycoprotein species selectively incorporated in the plasma membrane in the course of differentiation. As groundwork for such studies, we have investigated the synthesis and processing of T L molecules, whose expression might be expected to depend on appropr ia te association with/~-2-microglobulin (11, 12) as well as a prescribed sequence of posttranslational glycosylation steps which is doubtless a general feature of the synthesis of cell-surface glycoproteins (13-17). High resolution gel electrophoresis was used to resolve different T L species obtained from lactoperoxidase-iodinated cells, in which the label is confined to molecules accessible