CD8-BETA CHAIN INFLUENCES CD8-ALPHA CHAIN-ASSOCIATED LCK KINASE-ACTIVITY

The CD8 molecule plays an important role in the differentiation of CD8 (+) T cells in the thymus and in their normal function in the peripher y. CD8 exists on the cell surface in two forms, the alpha alpha homodi mer and the alpha beta heterodimer. Recent studies indicate an importa nt role for the CD8 beta chain in thymic development of CD8(+) T cells and suggest that signaling via CD8 alpha beta may be distinct from CD 8 alpha alpha. To better understand these differences, we introduced t he CD8 beta gene into a T cell hybridoma which only expressed the CD8 alpha alpha homodimer. In the parent hybridoma, cross-linking of the C D8 alpha chain led to minimal enhancement of CD8-associated Lck tyrosi ne kinase activity. In the CD8 beta(+) transfectants, several observat ions suggested that CD8 beta modifies CD8 alpha-associated Lck tyrosin e kinase activity: (a) in in vitro kinase assays, antibody-mediated cr osslinking of CD8 alone, or CD8 cross-linking with the TCR, resulted i n 10-fold greater activation of Lck kinase activity, compared to cells expressing CD8 alpha alpha alone; (b) in vivo, markedly enhanced tyro sine phosphorylation of several intracellular proteins was observed up on CD8 cross-linking with the TCR in CD8 alpha beta-expressing cells, compared to cells expressing CD8 alpha alpha alone; and (c) Lck associ ation with CD8 alpha was stabilized by the coexpression of CD8 beta. T hus, the differential Lck kinase activation and tyrosine phosphorylati on seen with CD8 alpha alpha vs. CD8 alpha beta may reflect the unique signaling capabilities of the CD8 beta molecule. These differences in signaling may, in part, account for the diminished ability to generat e CD8 single positive thymocytes in mice bearing a homozygous disrupti on of the CD8 beta gene.