PMID- 7983074
OWN - NLM
STAT- MEDLINE
DCOM- 19950104
LR  - 20210212
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 269
IP  - 49
DP  - 1994 Dec 9
TI  - Identification and immunological characterization of the domain of Actinobacillus 
      actinomycetemcomitans leukotoxin that determines its specificity for human target 
      cells.
PG  - 31289-95
AB  - Although extensive amino acid homology exists among the various Repeats in ToXin 
      (RTX) family of bacterial cytolysins, the cellular and species specificities 
      remain unique for individual toxins (i.e. Actinobacillus actinomycetemcomitans 
      leukotoxin (LtxA) kills human monomyelocytes while a related toxin, Pasteurella 
      hemeolytica leukotoxin (LktA) kills bovine lymphoid cells). To determine the Ltx 
      domain responsible for species specificity, ltxA/lktA chimeric toxin genes were 
      expressed in tandem with the ltxC gene under control of the P lambda promoter. 
      The ability of lysates to kill either HL-60 (human) or BL-3 (bovine) cells was 
      assessed by trypan blue exclusion. The critical area required for the chimeric 
      toxins to recognize human target cells is a 253-amino acid fragment (residue 
      688-941) that contains the GGXGXDX(L[I[V[W[Y[F)X repeats. A panel of 12 
      neutralizing anti-LtxA monoclonal antibodies also recognized specificities within 
      the 253-amino acid fragment. Epitope mapping of the monoclonal antibody panel 
      showed that all antibodies bound to one of three sites on the LtxA molecule. One 
      monoclonal recognized epitope A which was composed of LtxA residues 698-709 
      (KLDYYYTNKGFK), six antibodies recognized epitope B, a peptide composed of 
      residues 746-757 (LIYGYDGDDRLY), whereas the remaining five monoclonals 
      recognized epitope C, which is composed of residues 926-937 (DRARLKRQFELQ).
FAU - Lally, E T
AU  - Lally ET
AD  - Leon Levy Research Center for Oral Biology, University of Pennsylvania, School of 
      Dental Medicine, Philadelphia 19104-6002.
FAU - Golub, E E
AU  - Golub EE
FAU - Kieba, I R
AU  - Kieba IR
LA  - eng
GR  - DE07118/DE/NIDCR NIH HHS/United States
GR  - DE08239/DE/NIDCR NIH HHS/United States
GR  - DE09517/DE/NIDCR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Bacterial Toxins)
RN  - 0 (Exotoxins)
RN  - 0 (leukotoxin)
SB  - IM
GS  - lktA
GS  - ltxA
GS  - ltxC
MH  - Aggregatibacter actinomycetemcomitans/genetics/*metabolism
MH  - Amino Acid Sequence
MH  - Animals
MH  - Antibodies, Monoclonal/pharmacology
MH  - Bacterial Toxins/*genetics/immunology/metabolism
MH  - Base Sequence
MH  - Cattle
MH  - Chimera
MH  - Exotoxins/antagonists & inhibitors/*genetics/immunology/metabolism
MH  - Humans
MH  - Molecular Sequence Data
MH  - Sequence Homology, Amino Acid
MH  - Tumor Cells, Cultured
EDAT- 1994/12/09 00:00
MHDA- 1994/12/09 00:01
CRDT- 1994/12/09 00:00
PHST- 1994/12/09 00:00 [pubmed]
PHST- 1994/12/09 00:01 [medline]
PHST- 1994/12/09 00:00 [entrez]
AID - S0021-9258(18)47421-2 [pii]
PST - ppublish
SO  - J Biol Chem. 1994 Dec 9;269(49):31289-95.