VACCINATION OF THE LEISHMANIA-MAJOR SUSCEPTIBLE BALB C MOUSE .1. THE PRECISE SELECTION OF PEPTIDE DETERMINANT INFLUENCES CD4+ T-CELL SUBSETEXPRESSION/

BALB/c mice are susceptible to cutaneous leishmaniasis upon infection with Leishmania major while C57BL/6 are not. There is a major promasti gote surface protease (PSP or gp63) which is available in both native and recombinant forms, and for which the primary amino acid sequence i s known. Immunization with PSP has been shown to off er some protectio n against challenge with the live organism. Therefore, we attempted to develop a peptide vaccine with PSP peptides. in the first experiments , recall proliferative responses to PSP were measured using a set of 1 5mer peptides spanning the entire PSP molecule which allowed designati on of major determinant regions in BALB/c, C57BL/6, and CBA mice. Seve ral of these determinants were promiscuous and shared almost the ident ical core amino acid residues in the different strains. immunization w ith major determinant peptides was recalled vigorously with L. major s oluble antigen as well as with PSP. The response to peptide was almost entirely T(h)1 as measured by a localized ELISA assay for single-cell production of IFN-gamma. A similar assay for IL-5, which overcomes pr oblems of sensitivity and inhibition by lymphokines produced by T(h)1 cells, indicates very little production of T(h)2 cells even by BALB/c. It was found that if a major responsive peak was examined by recall w ith overlapping peptides, the highest, central peptide gave a mainly T (h)1 response while the boundary, less efficient peptides gave more of a T(h)2 response. Possible reasons for this were discussed. These res ults point to the importance of selecting the exactly appropriate pept ide in considering a vaccinogen that might protect susceptible individ uals. Even the choice of a somewhat immunogenic peptide within the det erminant envelope might actually exacerbate infection by steering the response in a T(h)2 direction.