PARASITE STRAIN SPECIFICITY OF BOVINE CYTOTOXIC T-CELL RESPONSES TO THEILERIA-PARVA IS DETERMINED PRIMARILY BY IMMUNODOMINANCE

The parasite strain specificity of CTL responses to Theileria parva va ries among cattle immunized with the same parasite stock. We have inve stigated the influence of class I MHC on the strain specificity of CTL responses to T. parva in 19 cattle of defined class I phenotype immun ized with either of two T. parva populations, in which protection to s ubsequent reciprocal challenge correlated with CTL strain specificity, In the majority of animals the response was restricted by the product s of one MHC haplotype and there was a consistent bias to some haploty pes in preference to others. In 10 of 13 cattle expressing the molecul arly defined MHC specificities A10 and KN104 on one haplotype, the CTL response was restricted entirely by this haplotype, thus allowing a p recise analysis of the MHC restriction specificities. The MHC restrict ion specificity and the parasite population used for immunization both influenced the strain specificity of the response. By examining respo nses in identical twins immunized with different parasites or in anima ls before and after challenge with heterologous parasites, animals tha t mounted a strain-specific response to primary infection were shown t o be capable of responding to Ags shared by the two parasite populatio ns. These findings indicate that the strain specificity of CTL respons es to T. parva is not determined primarily by immune response genes th at define the inherent capacity to respond, but rather is a consequenc e of the response in individual animals being biased toward a limited number of immunodominant peptide-MHC determinants.