H-2 compatibility requirement for virus-specific T-cell-mediated cytolysis. Evaluation of the role of H-2I region and non-H-2 genes in regulating immune response.

Abstract

Lymphocytic choriomeningitis virus (LCMV) and ectromelia virus-specific T-cell-mediated cytotoxicity was assayed in various strain combinations using as targets peritoneal macrophages which have been shown to express Ia antigens. Virus-specific cytotoxicity was found only in H-2K- or D-region compatible combinations. I-region compatibility was not necessary nor alone sufficient for lysis. Six different I-region specificities had no obvious effect on the capacity to generate in vivo specific cytotoxicity (expressed in vitro) associated with Dd. Low LCMV-specific cytotoxic activity generated in DBA/2 mice was caused by the non-H-2 genetic background. This trait was inversely related to the infectious virus dose and recessive. Non-H-2 genes, possibly involved in controlling initial spread and multiplication of virus, seem to be, at least in the examples tested, more important in determining virus-specific cytotoxic T-cell activity in spleens than are Ir genes coded in H-2.

Cell-Mediated Immunity to Vesicular Stomatitis Virus Infections in Mice

“…All these parameters are compatible with those found previously for T cell-mediated cytotoxic activity generated during infections with arenavirus [8,[35][36][37][38][39][40], poxvirus [3 ,4 ,1 1 ,1 2 ], myxo-and paramyxoviruses [7][8][9]34], and some tumor-associated viruses (Friend [5], murine sarcoma virus [13] 1 Metabolic inhibitors were added with the virus or later at the times indicated and were present during the test. The cytotoxicity was assayed during 3 h at 37 °C starting 180 min after initiation of the target cell infection.…”

“…This has been observed for other viruses; e.g., DBA/2 mice, which were low responders when infected with VSV, reacted similarly to LCMV [40]. The possibility that these differences are determined mainly by properties of macrophages is still open to investigation.…”

Multiple H-2-linked immune response gene control of H-2D- associated T-cell-mediated lympholysis to trinitrophenyl-modified autologous cells: Ir-like genes mapping to the left of I-A and within the I region

“…These results suggest a functional involvement by products of genes mapping within different H-2 regions in the generation of cytotoxic effector cells, irrespective of whether the dual recognition or altered self models (2) are considered. The failure to detect H-2-1inked,/r-like genetic effects in some of the viral° infected models (22) could be due to the complex and possible multiple specificities associated with a particular H-2 region product. Chemical modification of autologous cell surface products might provide a simpler model to detect H-2linked immune response genetic influences than the modifications resulting from complex biological interactions between virus and host.…”

The Influence of Non‐mhc Genes on the Cytotoxic T Cell Response to Modified Self

“…These genes, located in the K, D region, control Tc cells directly and genes located in the / region control T helper cells, themselves necessary for the amplification of a Tc cell response (Ashman and Mullbacher, 1979). Little is known regarding genes outside the H-2 complex and their effect on the Tc cell response; however, some evidence for non-MHC influence on viral Tc cells has been reported (Zinkernagel et al, 1976). The influence of non-MHC genes on a number of other immunological phenomena has been well documented (Dietz et al, 1981;Zaleski and Klein, 1978).…”