CD 8 / ~ Chain Influences CD 8 ol 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 periphery. CD8 exists on the cell surface in two forms, the olcr homodimer and the ol3 heterodimer. Recent studies indicate an important role for the CD8fl chain in thymic development of CD8 + T cells and suggest that signaling via CD8ol3 may be distinct from CDSo~a. To better understand these differences, we introduced the CD83 gene into a T cell hybridoma which only expressed the CDScca homodimer. In the parent hybridoma, cross-linking of the CDSol chain led to minimal enhancement of CDS-associated Lck tyrosine kinase activity. In the CD83 + transfectants, several observations suggested that CD83 modifies CD8ol-associated Ink tyrosine kinase activity: (a) in in vitro kinase assays, antibodymediated crosslinking of CD8 alone, or CD8 cross-linking with the TCR, resulted in 10-fold greater activation of l.ck kinase activity, compared to cells expressing CD8cxcx alone; (b) in vivo, markedly enhanced tyrosine phosphorylation of several intracellular proteins was observed upon CD8 cross-linking with the TCR in CD8oeB-expressing cells, compared to cells expressing CD8o~ca alone; and (c) Ink association with CDSo~ was stabilized by the coexpression of CD813. Thus, the differential Lck kinase activation and tyrosine phosphorylation seen with CD8cr162 vs. CD8cr may reflect the unique signaling capabilities of the CDSB molecule. These differences in signaling may, in part, account for the diminished ability to generate CD8 single positive thymocytes in mice bearing a homozygous disruption of the CD8B gene.