Harry W. Snyder

Blocking (suppressor) factors, immune complexes, and extracorporeal immunoadsorption in tumor immunity

Some animal neoplasms, particularly many of those induced by chemical carcinogens, have tumor-specific transplantation antigens. These are detected by their ability to induce the rejection of tumors grafted onto properly immunized syngeneic hosts (Prehn and Main, 1957; Old and Boyse, 1964; Sjogren, 1965; K. E. Hellstrom and Brown, 1979), and the tumors expressing the antigens are commonly referred to as immunogenic. It is being debated whether “spontaneous” tumors, like most human tumors, have antigens that can be immunogenic in the native host (Klein and Klein, 1977; Hewitt et al., 1976; Hellstrom et al., 1983).

Oncoviral proteins as cellular antigens.

This review will be concerned with immunological recognition of proteins encoded by oncoviruses and the biological consequences of this recognition. We shall discuss virion structural proteins and variants of these gene products which do not actually reside on virions, as well as proteins specified by cellular genes which have become incorporated into oncoviral genomes and can cause the malignant transformation of host cells. A number of the proteins in question are to be found on the surface of cells. This circumstance is connected with the capacity of the viruses to bud from the plasma membrane, and, in the case of some transformation-related viral proteins, may have to do with the phenotype of transformation. Cell-surface location makes a protein an efficient antigen, provides a point of attack for immune surveillance mechanisms defending against malignancy, and facilitates serological analysis in vitro.

Association of the Transforming Proteins of the ST and GA Strains of Feline Sarcoma Virus and Their in Vitro Associated Protein Kinase Activities with Cellular Membranes

The translation products of the Snyder-Theilen (ST) and Gardner-Arnstein (GA) strains of feline sarcoma virus (FeSV), termed gag-fes proteins, are high molecular weight polyproteins containing different amounts of the amino terminus of the feline leukemia virus (FeLV) gag gene-coded precursor protein linked to a similar sarcoma virus-specific polypeptide. Both polyproteins are phosphoproteins with indistinguishable in vitro associated tyrosine-specific protein kinase activities. The polyproteins are extremely hydrophobic proteins which are intimately associated with the plasma membrane fraction of transformed cells. Approximately 10% of the proteins are modified by glycosylation and expressed on the cell surface where they are accessible to lactoperoxidase-mediated radio-iodination and trypsinization. Cell surface localization of the polyproteins does not appear to be necessary for transformation. However, preliminary evidence suggests that the amount of FeLV p30 sequences at the amino end of the proteins may have some effect on the intracellular distribution of the gag-fes polyproteins and on the phenotype of the transformed cell.

Immunological and Biochemical Characterization of HZ2 Feline Sarcoma Virus and Abelson Murine Leukaemia Virus Translation Products

The extent of homology between the translation products of the HZ2 strain of feline sarcoma virus (HZ2-FeSV) and the Abelson murine leukaemia virus (A-MuLV) was examined immunologically and biochemically. Antiserum prepared against the v-abl-encoded determinants of the A-MuLV polyprotein P120gag-abl was also found to precipitate specifically the 98K mol. wt. HZ2-FeSV protein (P98gag-abl). The basis for this immunological crossreactivity was indicated by the findings that the two proteins had at least six [35S]methionine-containing tryptic peptides and at least eight [35S]methionine-containing chymotryptic peptides in common. Each of the two proteins also had tryptic and chymotryptic peptides which were unique. Both proteins were associated with tyrosyl kinase activities which exhibited some similar biochemical properties in vitro. However, the HZ2-FeSV-associated activity was much more sensitive to competitive inhibition by nucleoside and deoxynucleoside diphosphates than was the A-MuLV-associated activity. These results suggest that, while the gag-abl translation products of these two independent isolates of transforming retrovirus are highly related structurally and functionally, the differences in structure contribute to differences in enzyme activity. Further comparative studies of these two proteins should play an important role in determining their roles in induction of two different types of malignancy: lymphosarcoma in the case of the A-MuLV protein and fibrosarcoma in the case of the HZ2-FeSV protein.