Inhibition of the complement membrane attack complex by the galactose-specific adhesion of Entamoeba histolytica.
The human complement system is an important early host defense against infection. Entamoeba histolytica activates the complement system but is resistant to killing by complement C5b-9 complexes deposited on the membrane surface. Our aim was to identify components of the amebic plasma membrane that mediate resistance to human complement C5b-9 by screening for neutralizing monoclonal antibodies. A monoclonal antibody was identified that abrogated amebic resistance to C5b-9, and the mAb was shown to recognize the parasite's galactose-specific adhesin. The purified adhesin bound to C8 and C9 and conferred C5b-9 resistance to sensitive ameba upon reconstitution; these activities of the adhesin were inhibited by the antiadhesin mAb. The E. histolytica adhesin shared sequence similarities and antigenic cross-reactivity with CD59, a membrane inhibitor of C5b-9 in human blood cells, suggesting both molecular mimicry and shared complement-inhibitory functions.
Braga
L L
LL
Department of Medicine, University of Virginia School of Medicine, Charlottesville 22908.
Ninomiya
H
H
McCoy
J J
JJ
Eacker
S
S
Wiedmer
T
T
Pham
C
C
Wood
S
S
Sims
P J
PJ
Petri
W A
WA
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000502:physiology; D018957:CD59 Antigens; D003185:Complement C8 / Q000502:physiology; D003186:Complement C9 / Q000502:physiology; D015938:Complement Membrane Attack Complex / Q000037:antagonists & inhibitors*; D004748:Entamoeba histolytica / Q000276:immunology*; D000939:Epitopes / Q000032:analysis; D005690:Galactose / Q000494:pharmacology*; D006801:Humans; D037102:Lectins; D008562:Membrane Glycoproteins / Q000276:immunology / Q000494:pharmacology* / Q000502:physiology; D008565:Membrane Proteins / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D015800:Protozoan Proteins / Q000276:immunology / Q000494:pharmacology*; D011817:Rabbits
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018957:CD59 Antigens; D003185:Complement C8; D003186:Complement C9; D015938:Complement Membrane Attack Complex; D000939:Epitopes; D037102:Lectins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D015800:Protozoan Proteins; C052452:galactose inhibitable adherence protein, Entamoeba histolytica; D005690:Galactose