Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - A single amino acid determines the specificity of a monoclonal antibody which inhibits Plasmodium chabaudi AS in vivo.
AU - McKean, Paul G.
AU - O'Dea, Keiran P.
AU - Brown, K. Neil
PY - 1993/12
Y1 - 1993/12
N2 - The in vivo inhibitory action of NIMP23, a monoclonal antibody raised against the rodent parasite Plasmodium chabaudi chabaudi AS, has previously been shown to be strain-specific, capable of delaying significantly the onset of P. c. chabaudi AS but not a P. c. chabaudi CB challenge parasitaemia. The epitope to which this mAb binds has been mapped to the second of two epidermal growth factor-like domains located at the C-terminus of the merozoite surface protein 1 (MSP-1) of P. c. chabaudi AS. The C-terminus region of the MSP-1 of P. c. chabaudi is a region of heterogeneity with AS and CB strain parasites showing only 78% identity at the amino acid level. The critical amino acid substitution which accounts for the strain specificity of the NIMP23 monoclonal antibody has now been identified. Polymerase chain reaction directed mutagenesis experiments demonstrate that a single proline to asparagine substitution at position 1722 in the primary amino acid sequence is sufficient to convert NIMP23-negative P. c. chabaudi CB expression constructs into NIMP23-positive clones whilst the converse substitution of an asparagine for a proline residue converts P. c. chabaudi AS expression constructs into NIMP23-negative clones.
AB - The in vivo inhibitory action of NIMP23, a monoclonal antibody raised against the rodent parasite Plasmodium chabaudi chabaudi AS, has previously been shown to be strain-specific, capable of delaying significantly the onset of P. c. chabaudi AS but not a P. c. chabaudi CB challenge parasitaemia. The epitope to which this mAb binds has been mapped to the second of two epidermal growth factor-like domains located at the C-terminus of the merozoite surface protein 1 (MSP-1) of P. c. chabaudi AS. The C-terminus region of the MSP-1 of P. c. chabaudi is a region of heterogeneity with AS and CB strain parasites showing only 78% identity at the amino acid level. The critical amino acid substitution which accounts for the strain specificity of the NIMP23 monoclonal antibody has now been identified. Polymerase chain reaction directed mutagenesis experiments demonstrate that a single proline to asparagine substitution at position 1722 in the primary amino acid sequence is sufficient to convert NIMP23-negative P. c. chabaudi CB expression constructs into NIMP23-positive clones whilst the converse substitution of an asparagine for a proline residue converts P. c. chabaudi AS expression constructs into NIMP23-negative clones.
KW - Malaria
KW - Plasmodium chabaudi chabaudi
KW - Merozoite surface protein 1
KW - Epitope mapping
KW - Epidermal growth factor
KW - Antigenic diversity
U2 - 10.1016/0166-6851(93)90110-J
DO - 10.1016/0166-6851(93)90110-J
M3 - Journal article
VL - 62
SP - 211
EP - 221
JO - Molecular and Biochemical Parasitology
JF - Molecular and Biochemical Parasitology
SN - 0166-6851
IS - 2
ER -