title: Identification of a human HLA-E-restricted CD8+ T cell subset in volunteers immunized with Salmonella enterica serovar Typhi strain Ty21a typhoid vaccine.
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 nonclassical 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, but not CD1-a, -b, or -c, on 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 IFN-gamma production. Increases in the net frequency of IFN-gamma 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-gamma production when exposed to infected targets, raising the possibility that this novel effector mechanism might contribute to host defense against intracellular bacterial infections.
authors.affiliation: Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Rosângela
authors.initials: R
authors.lastname: Salerno-Gonçalves
authors.forename: Marcelo
authors.initials: M
authors.lastname: Fernandez-Viña
authors.forename: David M
authors.initials: DM
authors.lastname: Lewinsohn
authors.forename: Marcelo B
authors.initials: MB
authors.lastname: Sztein
mesh_terms: D000328:Adult; D019138:Antibodies, Blocking / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000378:metabolism; D017951:Antigen Presentation / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000201:enzymology / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology / Q000378:metabolism; D001666:Binding Sites, Antibody; D017252:CD3 Complex / Q000096:biosynthesis; D019002:CD56 Antigen / Q000096:biosynthesis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000382:microbiology; D002460:Cell Line; D002461:Cell Line, Transformed; D003594:Cytoplasmic Granules / Q000201:enzymology / Q000276:immunology / Q000382:microbiology; D003601:Cytotoxicity Tests, Immunologic / Q000379:methods; D006680:HLA Antigens / Q000276:immunology* / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D018655:Lymphocyte Count; D008875:Middle Aged; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D011499:Protein Processing, Post-Translational / Q000276:immunology; D012485:Salmonella typhi / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000382:microbiology; D014436:Typhoid-Paratyphoid Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000097625:HLA-E Antigens
chemical_list: D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D017252:CD3 Complex; D019002:CD56 Antigen; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D010446:Peptide Fragments; D046988:Proteasome Endopeptidase Complex; D014436:Typhoid-Paratyphoid Vaccines; D000097625:HLA-E Antigens