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CD4+ T-helper lymphocyte responses against Babesia bigemina rhoptry-associated protein I.
Title | CD4+ T-helper lymphocyte responses against Babesia bigemina rhoptry-associated protein I. |
Publication Type | Journal Article |
Year of Publication | 1996 |
Authors | Rodriguez, SD, Palmer, GH, McElwain, TF, McGuire, TC, Ruef, BJ, Chitko-McKown, MG, Brown, WC |
Journal | Infect Immun |
Volume | 64 |
Issue | 6 |
Pagination | 2079-87 |
Date Published | 1996 Jun |
ISSN | 0019-9567 |
Keywords | Animals, Antibodies, Protozoan, Antigens, Protozoan, Babesia, Base Sequence, Cattle, CD4-Positive T-Lymphocytes, Cell Line, Cytokines, Immunization, Lymphocyte Activation, Molecular Sequence Data, Protozoan Proteins, Protozoan Vaccines |
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. |
Alternate Journal | Infect. Immun. |
PubMed ID | 8675310 |
PubMed Central ID | PMC174039 |
Grant List | AI 30136 / AI / NIAID NIH HHS / United States |