DELIVERY BY TRYPANOSOMA-CRUZI OF PROTEINS INTO THE MHC CLASS-I ANTIGEN-PROCESSING AND PRESENTATION PATHWAY

Class I MHC-restricted T cell responses have been shown to be critical for the development of immune resistance to Trypanosoma cruzi in mice . However, to date, no antigenic targets of this anti-parasite respons e have been characterized. We have analyzed the characteristics of pot ential T. cruzi CTL target molecules by expression of the model CTL ta rget molecule chicken OVA in different cellular compartments of T. cru zi. OVA (amino acids 139-385) was expressed as a secretory, cytoplasmi c, transmembrane, or glycosyl phosphatidylinositol-anchored protein in T. cruzi transfectants. Host cells infected with T. cruzi transfectan ts that secreted or released OVA, but not those producing cytoplasmic or transmembrane forms of OVA, could process and present OVA peptide v ia the class I MHC pathway, as indicated by the stimulation of OVA-spe cific CD8(+) T cell hybridomas and the cytolysis of host cells infecte d with OVA-secreting parasites by OVA-specific CTLs. In addition, infe ction of mice with OVA-secreting parasites elicited the production of OVA-specific CTLs. These studies demonstrate the ability to target pro teins to specific cellular compartments in T. cruzi using either trypa nosomal or mammalian signal sequences. Furthermore, these results sugg est that proteins secreted or released by T. cruzi in infected cells a re a major source of peptides for MHC class I presentation and for the generation of parasite-specific CTL.