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Infection and Immunity, March 2001, p. 1869-1875, Vol. 69, No. 3
Instituto de Investigaciones
Biotecnológicas, Universidad Nacional de San Martín, San
Martín,1 and Département
de Microbiología, Facultad de Medicina, Universidad de Buenos
Aires, Buenos Aires,2 Argentina;
Département of Immunology, International Centre for
Genetic Engineering and Biotechnology (ICGEB), Trieste,
Italy3; and Unité de Biochimie
Structurale, CNRS URA 2185, Institut Pasteur, Paris,
France4
Received 9 June 2000/Returned for modification 4 August
2000/Accepted 14 November 2000
Trypanosoma cruzi, the agent of Chagas'
disease, expresses trans-sialidase, a unique enzyme
activity that enables the parasite to invade host cells by transferring
sialyl residues from host glyconjugates to the parasite's surface
acceptor molecules. The enzyme is also shed into the surrounding
environment, causing apoptosis in cells from the immune system.
During infections, an antibody response against the catalytic region of
the trans-sialidase that is coincident with the control
of the parasitemia and survival of the host is observed. This low-titer
humoral response is characterized by its persistence for many years in
benznidazole-treated patients. Here we analyzed the antigenic structure
of the molecule by phage-displayed peptide combinatorial libraries and
SPOT synthesis. Several epitopes were defined and located on the
three-dimensional model of the enzyme. Unexpectedly, cross-reaction was
found among several epitopes distributed in different locations
displaying nonconsensus sequences. This finding was confirmed by the
reactivity of three monoclonal antibodies able to recognize
non-sequence-related peptides that together constitute the surface
surrounding the catalytic site of the enzyme. The presence of
cross-reacting epitopes within a single molecule suggests a mechanism
developed to avoid a strong humoral response by displaying an undefined
target to the immune system.
0019-9567/01/$04.00+0 DOI: 10.1128/IAI.69.3.1869-1875.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Epitope Mapping of trans-Sialidase from
Trypanosoma cruzi Reveals the Presence of Several
Cross-Reactive Determinants
*
Corresponding author. Mailing address: Instituto
de Investigaciones Biotecnológicas, Universidad
Nacional de San Martín, Predio INTI, Edificio 24, Av. Gral Paz
y Constituyentes, 1650 San Martín, Buenos Aires, Argentina.
Phone: 54-11-45807255, 54-11-45807256, or 54-11-45807257. Fax: 54-11-47529639. E-mail:
oscar{at}iib.unsam.edu.ar.
Infection and Immunity, March 2001, p. 1869-1875, Vol. 69, No. 3
0019-9567/01/$04.00+0 DOI: 10.1128/IAI.69.3.1869-1875.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
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