The specificity of H-2-restricted cytotoxic T lymphocytes directed to AKR/Gross leukemia virus-induced tumors. II. Altered gp70 display and production of noninfectious virus particles by an insusceptible variant tumor

Eur J Immunol. 1983 Nov;13(11):871-7. doi: 10.1002/eji.1830131103.

Abstract

Derived from the susceptible AKR.H-2bSL1 tumor cell line, a variant tumor subclone, cl.18-5, was selectively insusceptible to H-2-restricted anti-AKR/Gross virus cytotoxic T lymphocytes (CTL) due to its failure to be recognized. In this study, the expression of virus-related products by variant cl.18-5 cells was compared to that of AKR.H-2bSL1 cells and a susceptible clone, as an approach towards defining the virus-associated antigens recognized by anti-AKR/Gross virus CTL. Despite the type specificity of the CTL, cl.18-5 displayed normal levels of the group-specific antigen (gag) encoded proteins p30, p15, p12 and p10, and the gag-associated Gross cell surface antigen. These results were confirmed by fluorescence-activated cell sorter analysis employing monoclonal antibodies specific for either AKR p12 or the cell surface glycosylated form of AKR ecotropic gag product. In contrast, cl.18-5 was variably less sensitive than AKR.H-2bSL1 to the action of complement and xenogeneic antisera directed against the envelope (env) product gp70. In addition, a panel of five monoclonal antibodies to gp70, which detect distinct endogenous ecotropic viral determinants, lysed AKR.H-2bSL1, but not cl.18-5 cells. However, absorption experiments indicated that cl.18-5 did express near normal levels of these specificities, suggesting an alteration in the orientation or topographical distribution of these determinants. Consistent with an inappropriate display of env products, cl.18-5 was found to be deficient in the production of infectious ecotropic leukemia virus. The particulate fraction of the cell-free supernatant of cl.18-5 contained normal levels of reverse transcriptase activity, indicating that noninfectious viral particles were being produced. Collectively, these results point to an association between recognition by anti-AKR/Gross virus CTL and the expression of ecotropic gp70 required for infectivity of virus.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • AKR murine leukemia virus / growth & development
  • AKR murine leukemia virus / immunology
  • Animals
  • Antigens, Viral / genetics
  • Antigens, Viral / immunology
  • Cell Line
  • Epitopes
  • Genetic Code
  • Genetic Variation
  • H-2 Antigens / genetics*
  • H-2 Antigens / immunology
  • Immunity, Innate
  • Leukemia, Experimental / etiology
  • Leukemia, Experimental / genetics
  • Leukemia, Experimental / immunology*
  • Mice
  • Mice, Inbred AKR
  • Mice, Inbred C57BL
  • Mink
  • Rabbits
  • Rats
  • T-Lymphocytes, Cytotoxic / immunology*
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / immunology*

Substances

  • Antigens, Viral
  • Epitopes
  • H-2 Antigens
  • Viral Envelope Proteins