Isolation of a feline leukaemia provirus containing the oncogene myc from a feline lymphosarcoma

The molecular mechanism by which feline leukaemia virus (FeLV) induces lymphoid malignancy in domestic cats is largely unknown. Using the insertional activation model of c-myc by avian leukosis virus in the induction of bursal lymphoma in chickens, we have now characterized the c-myc locus in feline tissues and investigated the possibility that FeLV may also insert within feline c-myc. We used the 1.5 kilobase (kb) PstI fragment of MC29 v-myc in Southern blot analysis to characterize the structure of the c-myc locus in the DNA of 31 naturally occurring feline lymphomas. Analysis of a cloned c-myc gene from one lymphoma demonstrated that sequences homologous to v-myc occupy 2.6 kb of feline DNA in which a putative intron of 0.5 kb separates sequences homologous to the 5' and 3' exons represented in avian v-myc. We also observed in the DNA of this lymphoma tumour-specific fragments homologous to v-myc. Characterization of these molecularly cloned myc-hybridizing fragments revealed the presence of at least two identical FeLV proviruses 5.5 kb in length, each containing long terminal repeats enclosing a spliced version of the feline myc gene.     

Multiple tumour-specific antigens expressed on a single tumour cell

Tumours induced by physical or chemical carcinogens often express tumour-specific antigens that can induce strong protective immune defence in the host. The diversity of these unique antigens among different tumours is seemingly endless, and has been compared to that of immune receptors. At present, the nature and complexity of this antigenicity is not known for any single tumour. Here we describe the unique antigenicity expressed by a murine ultraviolet light (UV)-induced fibrosarcoma. This tumour is clearly subject to immune surveillance by the normal host, and does not grow progressively unless it undergoes antigenic changes. Using defined monoclonal T-cell probes and tumour variants selected in vitro with these probes, we found that the total antigenicity consisted of multiple independent components, all of which were tumour-specific and expressed simultaneously on the same tumour cell. The demonstration of this antigenic complexity will enable us to identify and compare the molecular composition of the components of this antigen, as well as to determine their individual roles in tumour rejection and escape.     

The CD2 antigen associates with the T-cell antigen receptor CD3 antigen complex on the surface of human T lymphocytes

T lymphocytes can be activated by various stimuli directed either against the T-cell antigen receptor-CD3 antigen complex (Ti-CD3) or the CD2 molecule; see ref. 1 for a review. Activation signals generated by antigen binding to the antigen-specific alpha/beta heterodimer (Ti) are thought to be transduced via the invariant CD3 gamma, epsilon and delta chains, and the associated zeta and eta subunits. The physiological role of the interaction of CD2 with its homologous cell-surface associated ligand LFA-3 remains to be fully elucidated. It has been suggested that CD2 regulates an antigen-independent pathway of activation or that signals delivered via CD2 are an integral part of the antigen-specific pathway. Several recent studies have indicated a requirement for the Ti-CD3 complex in CD2 signalling. Thus, mutant T-cell lines expressing CD2, but not Ti-CD3, on the cell surface cannot be activated via the CD2 molecules. Functional interaction between the Ti-CD3 complex and the CD2 antigen suggests that these T-lymphocyte cell-surface structures are physically associated. Here we use a digitonin-based solubilization procedure to explore this possibility and show that 40% of the cell-surface CD2 molecules can be specifically co-precipitated in association with the Ti-CD3 complex.     

Transient expression of a surface antigen on a small subset of neurones during embryonic development

During development, neurones find and interconnect with their targets in a remarkably precise way. The unfolding of neuronal specificity involves a series of highly specific recognition events which are likely to be coordinated by the spatial and temporal expression of many different surface molecules. At early stages of development, neuronal recognition occurs most dramatically at the tips of growing axons, at growth cones and their filopodia. Previous studies on the grasshopper embryo suggest that specific filopodial contacts lead to the stereotyped patterns of selective axonal fasciculation; these results support the 'labelled pathways' hypothesis which predicts that the different neighbouring axon fascicles in the embryonic neuropil within filopodial grasp are differentially labelled. To uncover the molecular labels on fasciculating embryonic axons, we screened 2,000 monoclonal antibodies generated against the embryonic neuroepithelium. Here we describe three antibodies which reveal surface antigens whose temporal and spatial expression during embryogenesis correlate with the predictions of the model. In particular, the Mes-2 antibody recognizes an antigen which is transiently expressed on the surface of only 4 out of approximately 1,000 neurones in each metathoracic hemisegment during a short period of embryogenesis. The growth cones of two of these neurones fasciculate in the periphery and innervate the same target. Moreover, they transiently express the Mes-2 surface antigen while doing so.