Genetics of resistance to the African trypanosomes. III. Variant-specific antibody responses of H-2-compatible resistant and susceptible mice.

Genetically based differences in variant-specific immunity to the African trypanosomes were examined. H-2-compatible inbred mouse strains that differed in relative resistance were infected with Trypanosoma rhodesiense clone LouTat 1. Antibody responses to exposed epitopes of the LouTat 1 variant-specific surface glycoprotein (VSG) were measured. Relatively resistant B10.BR mice (H-2k) made predictable IgM antibody responses to the VSG of LouTat 1 which were associated with clearance of the LouTat 1 variant antigenic type from blood; IgG responses to LouTat 1 surface antigen appeared after clearance occurred, and were lower than peak titers of IgM. Intermediately susceptible CBA mice (H-2k) also made predictable IgM and IgG responses which followed the same pattern as the more resistant strain. Peak titers were lower for both Ig classes, however, and a delayed appearance of antibody was correlated with delayed clearance of LouTat 1. In contrast to B10.BR and CBA mice, the susceptible C3H mice (H-2k) failed to make detectable antibodies to LouTat 1 surface antigen and also failed to control the first peak of parasitemia. The absence of immunity in infected C3H mice was selective for antibody to exposed epitopes of LouTat 1 VSG because antibody was detectable to invariant VSG or internal trypanosome antigens. Also, the C3H strain was shown not to be a genetic nonresponder to LouTat 1 surface antigen because VSG-specific antibodies appeared within 1 wk after trypanocidal chemotherapy. Finally, we demonstrated that the susceptibility of C3H mice was not associated with an inability of the mononuclear phagocyte system to clear the parasites because drug cure, passive transfer of immune serum, or sensitization of trypanosomes with antibody all led to trypanosome clearance from blood by the liver. In summary, we show for the first time that major differences in variant-specific immunity occur in MHC-compatible animals after infection with the African trypanosomes.