Intratypic and intertypic specificity of lymphocytes involved in the recognition of herpes simplex virus glycoproteins

Abstract

Cytotoxic T lymphocytes (CTL) were generated in C57BL/6 mice with herpes simplex virus type 1 (HSV-1) (strains KOS, 17, HFEM, and mP) and HSV-2 (strains 186, G, and GP6). Effector lymphocytes were tested for cytotoxicity against syngeneic HSV-1-and HSV-2-infected cells in a 5-h 51Cr release assay. HSV-1 strain HFEM was found to induce CTL efficiently only when 100-fold more virus was used as compared with HSV-1 strains KOS, 17, and mP. All HSV-1 and HSV-2 strains induced cross-reactive populations of CTL. CTL generated by HSV-1 KOS and HSV-2 186 also demonstrated cross-reactivity in an earswelling model for delayed-type hypersensitivity. Lymphocytes generated by all HSV-2 strains were highly efficient at lysing HSV-1-infected target cells. However, HSV-2-infected target cells were found to be less susceptible to lysis by either HSV-1 or HSV-2 CTL than were HSV-1-infected target cells. The lowered susceptibility of HSV-2-infected cells was not due to an inefficient infection of BL/ 6 WT-3 cells as measured by standard growth assays and infectious center assays. Varying the multiplicity of infection or the time of infection did not increase the susceptibility of HSV-2-infected target cells to lysis by CTL. Increasing the effector-to-target-cell ratio resulted in an increased lysis of both HSV-1and HSV-2-infected target cells by CTL, but the level of HSV-2-infected target cell lysis still did not approach the level of HSV-1-infected target cell lysis. HSV-2-infected cells were as efficient as HSV-1-infected cells in the cold cell competition assay employed in reducing the lysis of 51Cr-labeled, HSV-1-infected target cells. In addition, HSV-2-infected cells were susceptible to lysis by HSV-immune serum and complement.

Cells expressing herpes simplex virus glycoprotein gC but not gB, gD, or gE are recognized by murine virus-specific cytotoxic T lymphocytes

“…The involvetnent of HSV glycoproteins as the major viral antigenic determinants seen by CTL was suggested by studies which demonstrated that target cells infected with temperature-sensitive mutants of HSV which expressed reduced amounts of cell surface viral glycoproteins at the nonpermissive temperature and target cells treated with known inhibitors of glycosylation showed reduced susceptibility to HSV-specific CTL (5,20). Furthermore, as has been shown for a number of viruses (48), infection with one serotype of HSV results in the generation of cross-reactive CTL capable of lysing syngeneic target cells infected with a distinct serotype of HSV (4,11). This suggested that both type-specific and type-common viral determinants were recognized by HSV-specific CTL.…”

Human herpesviruses: a consideration of the latent state.

“…Thus, skin, mucous membranes, and corneal epithelium are all commonly involved, with gingivostomatitis being the most common clinical manifestation of HSV-1 disease following initial infection. Often, however, there is an initial subclinical infection of one of these areas (usually the mouth) and the subsequent appearance of a protective, specific immune response which includes neutralizing antibodies, which are directed against glycoproteins present in the viral envelope, and cytotoxic T cells, which (if the human infection mirrors the murine model) are directed against both envelope and nonstructural proteins (10,68). The events occurring with HSV-2 are similar, but the skin of the genital area and the vaginal mucous membranes are the sites of initial infection.…”

Herpes simplex virus type 1-specific cytotoxic T lymphocytes recognize virus nonstructural proteins

“…However, the precise specificity of the CTL response to viral antigens remains undetermined for many viruses. In fact, earlier studies in this area assumed that viral glycoproteins expressed in large amounts upon the infected cell surface were the target antigens for CTL (4,9,12,13,15).…”