Joint recognition by cytotoxic T cells of inactivated Sendai virus and products of the major histocompatibility complex.

Abstract

Cytotoxic T cells specific for Sendai virus were generated by culturing murine spleen cells in vitro together with UV-inactivated Sendai virus. In vivo immunization of donor mice with UV-inactivated Sendai virus resulted in an in vitro secondary response of increased magnitude. Cytotoxic activity was demonstrated in a short-term 51Cr-release assay, using syngeneic tumor cells which had been coated with inactivated Sendai virus by incubation at 4 degrees C for 30 min. The lysis of Sendai virus-coated target cells was restricted by the H-2 haplotype of the target cells, suggesting that the H-2 genes of the target cell contributed to the specificity of the lysis. Kinetic experiments showed that susceptibility to lysis by cytotoxic T cells specific for Sendai virus appeared within 30 min after coating target cells with inactivated virus. Furthermore, there was no detectable synthesis of new proteins in cells treated with UV-inactivated Sendai virus. For these reasons, we suggest that neither viral replication nor the synthesis of new proteins are necessary for the production of the antigen recognized by cytotoxic cells specific for Sendai virus. We infer that the virus-specific component on the target cells is probably a preformed virion antigen adsorbed onto or integrated into the cell membrane. These results imply that, if the cytotoxic T cell recognizes a single antigenic determinant specified both by viral and H-2 genes, this determinant is formed by the physical association of H-2 and Sendai virus antigens rather than by their alteration during the processes of synthesis.

Generation of cytolytic T lymphocytes after reovirus infection: role of S1 gene.

“…It has also been demonstrated that active infection is not required for the induction of a CTL response to Sendai virus (25). However, sensitization of uninfected targets does not occur with UV-inactivated influenza virus (26), and other investigators suggested that synthesis of early viral proteins is needed for lysis of vaccinia-or ectromelia-infected targets (27,28).…”

Biological significance of alloreactivity: T cells stimulated by Sendai virus-coated syngeneic cells specifically lyse allogeneic target cells.

“…Spleen cells (7 X 106) were cultured in vttro for 5 days with 6 X 106 x-irradiated spleen stimulator cells as described (4). Virus-coated stimulator cells were prepared by a modification of the procedure described by Schrader and Edelman (5). After treatment with Tris/ NH4Cl and x-irradiation [1500 R (1 R = 2.58 X 10-4 C/kg), GE Maximar 250], 50 X 106 spleen cells were incubated with 0.01 ml of virus suspension for 90 min in 2 ml of culture medium and then washed to remove free virus particles.…”

Cytotoxic T-cell response to ectromelia virus-infected cells. Different H-2 requirements for triggering precursor T-cell induction or lysis by effector T cells defined by the BALB/c-H-2(db) mutation

“…Extensive experiments with five mutants of the H-2K b region and ectromelia, vaccinia, and lymphocytic choriomeningitis viruses (4,5,10,(14)(15)(16) have shown that a single gene in H-2K b, probably a cistron coding for an H-2 polypeptide antigen (17) makes an essential, direct contribution to the antigenic patterns recognized by Tc cells specific for H-2K ~ plus virus. Evidence from the H-2K b mutants (16) and recent work with Sendai virus (18) suggests that H-2 antigens become physically associated with viral antigens in infected cell membranes, but the way this happens is unclear. Therefore, another important feature of H-2 antigens may be their capacity to form compound or interaction antigens by associating with viral gene products (5,6,16,19,20).…”