Localization of Knops system antigens in the long homologous repeats of complement receptor 1

The Sl(a) (Knops system) located on complement receptor 1 (CR1) has been associated with malarial rosetting, a process associated with severe malarial infections. Moreover, the long homologous repeats (LHRs) B and C of CR1 were implicated in rosette formation. As a step toward mapping the location of Knops system antigens, truncated CR1 proteins have been expressed and their ability to inhibit antibodies to the high-incidence Knops system antigens was assessed.

Individual LHRs (A, B, C, and D) of CR1 of the common CR1*1 (F) allotype were expressed as secreted forms in 293T cells. Their abilities to specifically neutralize Knops system antibodies were tested by both hemagglutination and flow cytometry.

Three examples of anti-Kn(a) (n = 6) were almost completely inhibited by LHR-C and three by LHR-D. Two examples of anti-McC(a) (n = 2) and seven examples of anti-Sl(a) (n = 8) were inhibited by LHR-D. Both examples of anti-Yk(a) (n = 2) were partially inhibited by LHR-D.

The high-incidence Knops system antigens reside within LHR-D and to a lesser extent within LHR-C. Because of the role of Sl(a) antigen in malaria rosetting, these results indicate that LHR-D may represent an additional malaria interaction region in CR1.