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Infection and Immunity, June 2000, p. 3079-3089, Vol. 68, No. 6
Unité de Biologie des Régulations
Immunitaires1 and Unité de
Programmation Moléculaire et Toxicologie Génétique
(CNRS-URA1444),3 Institut Pasteur, Paris,
France, and Institute for Animal Science and Health
(ID-DLO), Lelystad, The Netherlands2
Received 1 July 1999/Returned for modification 23 November
1999/Accepted 14 March 2000
We analyzed the CD4 T-cell immunodominance of the response to a
model antigen (Ag), MalE, when delivered by an attenuated strain of
Salmonella enterica serovar Typhimurium (SL3261*pMalE). Compared to purified MalE Ag administered with adjuvant, the mapping of
the peptide-specific proliferative responses showed qualitative differences when we used the Salmonella vehicle. We
observed the disappearance of one out of eight MalE peptides' T-cell
reactivity upon SL3261*pMalE immunization, but this phenomenon was
probably due to a low level of T-cell priming, since it could be
overcome by further immunization. The most striking effect of
SL3261*pMalE administration was the activation and stimulation of new
MalE peptide-specific T-cell responses that were silent after
administration of purified Ag with adjuvant. Ag presentation assays
performed with MalE-specific T-cell hybridomas showed that infection of Ag-presenting cells by this intracellular attenuated bacterium did not
affect the processing and presentation of the different MalE peptides
by major histocompatibility complex (MHC) class II molecules and
therefore did not account for immunodominance modulation. Thus,
immunodominance of the T-cell response to microorganisms is governed
not only by the frequency of the available T-cell repertoire or the
processing steps in Ag-presenting cells that lead to MHC presentation
but also by other parameters probably related to the infectious process
and to the bacterial products. Our results indicate that, upon
infection by a microorganism, the specificity of the T-cell response
induced against its Ags can be much more effective than with purified
Ags and that it cannot completely be mimicked by purified Ags
administered with adjuvant.
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Extending the CD4+ T-Cell Epitope
Specificity of the Th1 Immune Response to an Antigen Using a
Salmonella enterica Serovar Typhimurium Delivery
Vehicle
*
Corresponding author. Mailing address: Institut
Pasteur, 25 rue du Docteur Roux, 75724 Paris cedex 15, France. Phone:
33.1.45.68.83.52. Fax: 33.1.45.68.85.40. E-mail:
rloman{at}pasteur.fr.
Infection and Immunity, June 2000, p. 3079-3089, Vol. 68, No. 6
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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