Activated T cells transcribe an alternatively spliced mRNA encoding a soluble form of Qa-2 antigen

Abstract

Among the best characterized non-classical mouse major histocompatibility antigens are the Qa-2 molecules. These proteins can serve as targets for allogenic cytotoxic T cells and as signal transducing molecules. They are structurally similar to H-2 transplantation antigens in their N-terminal and beta 2-microglobulin binding domains but differ at their C-termini. While the H-2 antigens span the cell membrane, the Qa-2 molecules are attached to the cell surface via phospholipid anchors. The genetic information encoding this attachment is contained in exon 5. In concanavalin A activated splenocytes the expression of membrane bound Qa-2 antigens declines and, simultaneously, soluble forms of Qa-2 molecules are secreted. We demonstrate here that the soluble Qa-2 polypeptides are translated from alternatively spliced mRNAs lacking exon 5, while the membrane forms are encoded by the full-size transcripts. In cultured cells the alternative splicing of the Qa-2 message is induced by T-cell activation splicing of the Qa-2 message is induced by T-cell activation with concanavalin A. The canonical mRNA encoding the membrane form of Qa-2 predominates in unstimulated mouse tissues but the cultured cell lines, like activated T cells, express enhanced levels of the truncated mRNA. In some cell lines almost all Qa-2 transcripts lack exon 5. For example, in L cells, mRNAs encoding soluble Qa-2 molecules are at least 10 times more abundant than Qa-2 transcripts encoding phospholipid anchored antigens. These findings are discussed in terms of potential functions of membrane bound and secreted Qa-2 molecules.