title: CD4+ T-helper lymphocyte responses against Babesia bigemina rhoptry-associated protein I.
abstract: A multigene family of 58- to 60-kDa proteins, which are designated rhoptry-associated protein 1 (RAP-1) and which come from the parasites Babesia bigemina and Babesia bovis, is a target for vaccine development. The presence of multiple gene copies and conserved sequences and epitopes of RAP-1 implies that these proteins are functionally important for the survival of these parasites. Furthermore, it was previously shown that B. bigemina RAP-1 induced partial protection against challenge infection. However, the lack of correlation between protective immunity to B. bigemina infection and antibody titers against a merozoite surface-exposed, neutralization-sensitive epitope of B. bigemina RAP-1 indicated the potential importance of RAP-1-specific T helper (Th) cells in the observed protection. To begin to understand the mechanism of RAP-1-induced protective immunity, RAP-1-specific T-cell responses were characterized in cattle. Vigorous and sustained proliferative responses of peripheral blood mononuclear cells from native RAP-1-immunized cattle were observed. The anamnestic response in immunized cattle was specific for B. bigemina RAP-1 and predominantly comprised CD4+ T cells, which upon cloning expressed type 1 cytokine mRNA profiles and high levels of gamma interferon protein. The T cells responded to both native and recombinant forms of RAP-1, indicating the potential to use recombinant protein or epitopes derived therefrom as a vaccine that could evoke specific recall responses after exposure to natural infection. The differential responses of peripheral blood mononuclear cells and seven Th-cell clones derived from RAP-1-immunized cattle to different Central American strains of B. bigemina indicated the presence of at least one conserved and one variable Th-cell epitope. The lack of response to B. bovis RAP-1 indicated that a strictly conserved 14-amino-acid peptide shared by the two babesial species was not immunogenic for Th cells in these experiments. However, the Th-cell epitope conserved among strains of B. bigemina may be a useful component of a RAP-1 subunit vaccine.
authors.affiliation: Department of Veterinary Pathobiology, Texas A&M University, College Station 77843, USA.
authors.forename: S D
authors.initials: SD
authors.lastname: Rodríguez
authors.forename: G H
authors.initials: GH
authors.lastname: Palmer
authors.forename: T F
authors.initials: TF
authors.lastname: McElwain
authors.forename: T C
authors.initials: TC
authors.lastname: McGuire
authors.forename: B J
authors.initials: BJ
authors.lastname: Ruef
authors.forename: M G
authors.initials: MG
authors.lastname: Chitko-McKown
authors.forename: W C
authors.initials: WC
authors.lastname: Brown
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000953:Antigens, Protozoan / Q000276:immunology*; D001403:Babesia / Q000276:immunology*; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002417:Cattle; D002460:Cell Line; D016207:Cytokines / Q000235:genetics; D007114:Immunization; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D015800:Protozoan Proteins / Q000276:immunology*; D016052:Protozoan Vaccines / Q000276:immunology
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D016207:Cytokines; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; C065352:rhoptry associated protein, Plasmodium