Bovine cytotoxic T-cell clones specific for cells infected with the protozoan parasite Theileria parva: parasite strain specificity and class I major histocompatibility complex restriction.

Abstract

We present information on the specificity of three bovine cytotoxic T-cell clones reactive with lymphoblasts infected with the protozoan parasite Theileriaparva. The clones were derived from peripheral blood mononuclear cells of an animal immunized with T. parva (Muguga stock), after five stimulations in vitro with an autologous parasitized cell line. The three clones belonged to the BoT8+ subset of T cells, which is similar to the human CD8' T-cell subset. On the basis of analysis on a panel of infected target cells originating from cattle of different major histocompatibility complex (MHC) phenotypes, killing by all three clones was found to be restricted to targets bearing the class I MHC specificity KN1O4, which is defined by alloantiserum KNA104 and monoclonal antibody IL-A4. This class I MHC restriction was confirmed by blocking of target cell lysis with these antibodies and monoclonal antibody w6/32, which reacts with a nonpolymorphic determinant on bovine class I MHC molecules. The three clones were parasite strain specific, in that they did not kill cells of the appropriate MHC type infected with T. parva (Marikebuni stock). These findings, taken together with previous observations that immunization of cattle with T. parva (Muguga) does not provide protection against challenge with T. parva (Marikebuni), suggest that the cytotoxic T cells recognize a cell surface antigen that may be important in induction ofimmunity to the parasite.

Extensive Polymorphism and Evidence of Immune Selection in a Highly Dominant Antigen Recognized by Bovine CD8 T Cells Specific for Theileria annulata

“…This is well established as an important phenomenon in infections with some RNA viruses that exhibit a high rate of mutation, most notably, HIV-1 (18,26,39). Parasite strain-restricted CD8 T cell responses have also been reported for several protozoan infections, including human malaria and theileriosis in cattle (15,17,35). In the case of Theileria parva, variation between animals in the strain specificity of CD8 T cell responses has been shown to correlate with incomplete cross-protection between parasite strains (54).…”

Characterization of the Fine Specificity of Bovine CD8 T-Cell Responses to Defined Antigens from the Protozoan ParasiteTheileria parva

“…The long duration of immunity to East Coast fever also contrasts with immunity to malaria, which develops only after several years of exposure and wanes in the absence of exposure to parasite challenge (9). The ability to culture the schizont stage of the parasite in continuously growing lymphoblastoid cell lines allows detailed in vitro analyses of T-cell responses to the whole parasite; this system has been used extensively to monitor responses in animals undergoing immunization and challenge and to examine the specificity of the responses (6,7,8,10,11,15,19,20).…”

Restriction mapping of the genome of the protozoan parasite Theileria parva.

“…Cell-mediated strain-specific immunity can be achieved by infection and simultaneous treatment with long-acting tetracycline (3,4). This implies antigenic polymorphism in the parasite and means that sexual recombination may be important in generating antigenic diversity in the field.…”