Protective immune responses as indicators of antigenic diversity and stability

By definition, the biology of a living organism must be characterized before its molecular biology can be interpreted. Malariologists are fortunate in that the malaria parasite was used as a well-controlled therapy for tens of thousands of hospital patients. During many of these treatments the opportunity was taken to study malaria and the behaviour of the parasite in detail. From these, and similar studies on volunteers, together with numerous epidemiological surveys, the operational characteristics of immunity to malaria in man have been well defined. Unfortunately this information, which exists in some detail in the older literature, does not seem to have been available to many investigators. This situation has led to interpretations of molecular data which are inconsistent with the known biology of the parasites and human-parasite relationships. This article considers how the structure of one of the best studied antigens, MSP1, can be viewed in the context of the host-parasite relationship. It postulates some testable hypotheses which aim to reconcile the molecular characteristics of the antigen with the biology and immunology of the asexual erythrocytic stage of the parasite.