ABSTRACT
We have previously found that the acquired protection against malaria implicates a mechanism of defense that relies on the cooperation between cytophilic antibodies and monocytes. Accordingly, an assay of antibody-dependent cellular inhibition (ADCI) of parasite growth was used as a means of selecting for molecules capable of inducing protective immunity to malaria. This allowed us to identify in the sera of clinically protected subjects an antibody specificity that promotes parasite killing mediated by monocytes. This antibody is directed to a novel merozoite surface protein (MSP-3) of a molecular mass of 48 kD. Purified IgG from protected subjects are effective in ADCI and those directed against MSP-3 are predominantly cytophilic. In contrast, in nonprotected individuals, whose antibodies are not effective in ADCI, anti-MSP-3 antibodies are mostly noncytophilic. A region in MSP-3 targetted by antibodies effective in the ADCI assay was identified and its sequence was determined; it contains an epitope not defined by a repetitive structure and does not appear to be polymorphic. Antibodies raised in mice against a peptide containing this epitope, as well as human antibodies immunopurified on this peptide, elicit a strong inhibition of Plasmodium falciparum growth in ADCI assay, whereas control antibodies, directed to peptides from other molecules, do not. The correlation between isotypes of antibodies produced against the 48-kD epitopes, clinical protection, and the ability of specific anti-MSP-3 antibodies to block the parasite schizogony in the ADCI assay suggests that this molecule is involved in eliciting protective mechanisms.
Subject(s)
Antibodies, Protozoan/immunology , Antigens, Protozoan/immunology , Immunoglobulin G/blood , Monocytes/immunology , Plasmodium falciparum/immunology , Protozoan Proteins/immunology , Amino Acid Sequence , Animals , Antibodies, Protozoan/analysis , Antibodies, Protozoan/biosynthesis , Antibodies, Protozoan/blood , Antibody Specificity , Base Sequence , Blotting, Western , DNA Primers , DNA, Protozoan/analysis , DNA, Protozoan/genetics , Fluorescent Antibody Technique , Humans , Immunoglobulin G/analysis , Immunoglobulin Isotypes/analysis , Immunoglobulin Isotypes/blood , Molecular Sequence Data , Peptides/chemical synthesis , Peptides/immunology , Polymerase Chain Reaction , Protozoan Proteins/analysis , Protozoan Proteins/biosynthesis , Recombinant Proteins/immunology , Sensitivity and SpecificityABSTRACT
We report the identification of a 48 kDa antigen targetted by antibodies which inhibit P. falciparum in vitro growth by cooperation with blood monocytes in an ADCl assay correlated to the naturally acquired protection. This protein is located on the surface of the merozoite stage, and is detectable in all isolates tested.
Subject(s)
Antigens, Protozoan/immunology , Antigens, Protozoan/isolation & purification , Immunization , Malaria, Falciparum/immunology , Plasmodium falciparum/immunology , Adult , Amino Acid Sequence , Animals , Antigens, Protozoan/chemistry , Base Sequence , HumansABSTRACT
The injection of streptozotocin in intact or adrenalectomized rats produced a decrease in the number of thymus lymphoid cells. Bovine serum albumin gradient analyses of thymocytes from control, adrenalectomized, adrenalectomized-diabetic and diabetic animals showed variations in the mature/immature cell ratio. No remarkable changes in the distribution of the different thymocyte subpopulations were observed.
Subject(s)
Adrenalectomy , Diabetes Mellitus, Experimental/pathology , Thymus Gland/pathology , Animals , Cell Fractionation , Male , Organ Size , Rats , StreptozocinABSTRACT
The injection of streptozotocin in intact or adrenalectomized rats produced a decrease in the number of thymus lymphoid cells. Bovine serum albumin gradient analyses of thymocytes from control, adrenalectomized, adrenalectomized-diabetic and diabetic animals showed variations in the mature/immature cell ratio. No remarkable changes in the distribution of the different thymocyte subpopulations were observed.
ABSTRACT
The injection of streptozotocin in intact or adrenalectomized rats produced a decrease in the number of thymus lymphoid cells. Bovine serum albumin gradient analyses of thymocytes from control, adrenalectomized, adrenalectomized-diabetic and diabetic animals showed variations in the mature/immature cell ratio. No remarkable changes in the distribution of the different thymocyte subpopulations were observed.
