An MHC-restricted CD8+ T-cell response is induced in cattle by foot-and-mouth disease virus (FMDV) infection and also following vaccination with inactivated FMDV

Abstract

Foot-and-mouth disease virus (FMDV) causes a highly contagious disease of cloven-hooved animals that carries enormous economic consequences. CD8 + cytotoxic T lymphocytes play an important role in protection and disease outcome in viral infections but, to date, the role of the CD8 + T-cell immune response to FMDV remains unclear. This study aimed to investigate major histocompatibility complex (MHC) class I-restricted CD8 + T-cell responses to FMDV in vaccinated and in infected cattle. An in vitro assay was used to detect antigen-specific gamma interferon release by CD8 + T cells in FMDV-infected cattle of known MHC class I genotypes.A significant MHC class I-restricted CD8 + T-cell response was detected to both FMDV strain O1 BFS and a recombinant fowlpox virus expressing the structural proteins of FMDV. Antigen-specific MHC class I-restricted CD8 + T-cell responses were also detected in cattle vaccinated with inactivated FMDV. These responses were shown to be directed, at least in part, to epitopes within the structural proteins (P12A region) of the virus. By using mouse cells expressing single cattle MHC class I alleles, it was possible to identify the restriction elements in each case. Identification of these epitopes will facilitate the quantitative and qualitative analysis of FMDV-specific memory CD8 + T cells in cattle and help to ensure that potential vaccines induce a qualitatively appropriate CD8 + T-cell response.

Induction of a Cross-Reactive CD8+T Cell Response following Foot-and-Mouth Disease Virus Vaccination

“…We have previously reported the identification of virus-specific memory CD8 ϩ T cells following infection with FMDV or vaccination with inactivated virus (28). In that study, we were unable to identify effector CD8 ϩ T cells ex vivo at week 6 or later after infection or vaccination.…”

“…Fowlpox recombinants expressing the polyprotein P1A, P1B, P1C, and P1D (VP4, VP2, VP3, and VP1, respectively) and including the nonstructural protein 2A of FMDV serotypes O and A were constructed as described previously (28). The O 1 Manisa and A 22 /Iraq vaccines were prepared from antigen concentrate stored over liquid nitrogen, which is being held at a commercial facility as part of a new United Kingdom strategic reserve.…”

Foot-and-Mouth Disease Virus Can Induce a Specific and Rapid CD4+T-Cell-Independent Neutralizing and Isotype Class-Switched Antibody Response in Naïve Cattle

“…We have also shown in separate studies that there is no generalized immunosuppression during the acute phase of FMDV infection in cattle or a loss of specific T-cell populations (data not shown). Capsid-induced T-cell recall responses are detectable after FMDV infection (12,28). However, we have also shown that an FMDV-specific CD4 T-cell response is not detectable for at least 12 days after FMDV infection (data not shown), making the analysis of FMDV-specific T-cell responses during the period of depletion of little value in the present study.…”

“…Recently, Guzman et al (28) used gamma interferon production to demonstrate virus-specific MHC class I-restricted CD8 ϩ T-cell re-sponses in cattle infected or vaccinated with FMDV, but the role of these CD8 ϩ T cells in immunity to FMDV infection is still not known. There is an abundant ␥␦ T-cell population in ruminants; however, there is no clear consensus on the role of these cells in immunity to infections (13,52).…”

Identification of Major Histocompatibility Complex Restriction and Anchor Residues of Foot-and-Mouth Disease Virus-Derived Bovine T-Cell Epitopes

“…However, an identification of binding motifs of particular peptides representing T-cell epitopes was not performed. The role of MHC class I-restricted CD8 ϩ T cells in the immune response to FMDV was addressed only recently (16). In this particular survey with MHC class I-typed animals, for the first time a gamma interferon (IFN-␥) response of sorted CD8 ϩ T cells against whole virus and recombinant protein consisting of P1 and 2A regions was shown.…”