Identification of a human HLA-E-restricted CD8+ T cell subset in volunteers immunized with Salmonella enterica serovar Typhi strain Ty21a typhoid vaccine

Rosângela Salerno-Gonçalves, Marcelo Fernandez-Viña, David M. Lewinsohn, Marcelo B. Sztein

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Abstract

Our previous studies in volunteers immunized with Salmonella enterica serovar Typhi (S. Typhi) have suggested an important role for CD8+ T cells in host defense. In this study we describe a novel subset of neoclassical human HLA-E-restricted S. Typhi-specific CD8+ T cells derived from PBMC of Ty21a typhoid vaccinees. CD3+CD8+CD4 -CD56- T cells effectively killed S. Typhi-infected targets regardless of whether they share classical HLA class I molecules with them, by a FAS-independent, granule-dependent mechanism, as evidenced by induction of granzyme B release and the blocking effects of concanamycin and strontium ions. The expression of HLA-E Ags, bat not CD1-a, -b, or -c, OB the membrane of S. Typhi-infected targets rendered them susceptible to lysis. Moreover, anti-HLA-E Abs partially blocked these responses. We also demonstrated that presentation of S. Typhi Ags via HLA-E could stimulate lFN-γ production. Increases in the net frequency of IFN-γ spot-forming cells were observed in the presence of targets coated with peptides that contain S. Typhi GroEL HLA-E binding motifs. These results demonstrate that HLA-E binds nonamer peptides derived from bacterial proteins and trigger CD8 +-mediated lysis and IFN-γ production when exposed to infected targets, raising the possibility that this novel effector mechanism might contribute to host defense against intracellular bacterial infections.

Original languageEnglish (US)
Pages (from-to)5852-5862
Number of pages11
JournalJournal of Immunology
Volume173
Issue number9
DOIs
StatePublished - Nov 1 2004

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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