SUMMARYMouse L cell lines have been developed which constitutively express glycoproteins B (gB) and D (gD) of herpes simplex virus type 1. When used to study the immune response of mice to the viral glycoproteins, it was found that both gB and gD induce a delayed type hypersensitivity response and both also induce an antibody response, but only the cell line expressing gD could stimulate the production of neutralizing antibody. Virus-specific cytotoxic T lymphocytes (CTLs) recognized gB expressed by the cell line and this line could also induce CTLs in mice. Recognition of gD by major histocompatibility complex class I restricted CTLs was never seen. Vaccination of mice with the cell lines provided protection from viral challenge and inhibited the establishment of a latent infection, although gD proved to be the better protective immunogen.
INTRODUCTIONThe immune response of mice to herpes simplex virus type 1 (HSV-1) is known to involve both antibody and cell-mediated protective mechanisms. In particular, T lymphocytes are considered to play a central role in the recovery from a primary infection (for review, see Nash et al., 1985). However, the particular proteins of the virus recognized by these cells are far from clear. Experiments to date have centred on the use of the virus mutants deficient in the expression of certain glycoproteins to study the nature of the antigens recognized by cytotoxic T lymphocytes (CTLs) (Carter et al., 1981;Lawman et al., 1980;Glorioso et al., 1985), and the affinity purification of glycoproteins from whole virus preparations for use as immunogens to study delayed type hypersensitivity (DTH) responses (Schrier et al., 1983;Chan et al., 1985).The main problem has been how to separate the various antigens of this complex virus in order to dissect the nature of the immune response. Our approach has been to investigate the immune response to individual glycoproteins of HSV-1 by expressing the appropriate genes in mouse L cells. In this system, the glycoproteins are expressed in isolation but are still presented at the cell surface analogous to infected cells. Our reason for choosing glycoproteins is that they are likely to represent major target antigens of the immune system: this is true for the antibody response (for review, see Norrild, 1985) and there is evidence to suggest that glycoproteins are the major targets for both major histocompatibility complex (MHC) class I and class II restricted T lymphocytes (Carter et al., 1981 ;Lawman et al., 1980;Glorioso et al., 1985;Schrier et al., 1983).In this paper we report the establishment of L cells expressing either glycoprotein B (gB) or D (gD) and the use of these lines to study the specificity of the T cell response to HSV-1. The lines were also used to immunize mice against primary virus infections and to prevent the establishment of latent infections.