Antimicrobial activity of MHC class I-restricted CD8+ T cells in human tuberculosis
AUTOR(ES)
Cho, Sungae
FONTE
The National Academy of Sciences
RESUMO
Studies of mouse models of tuberculosis (TB) infection have indicated a central role for MHC class I-restricted CD8+ T cells in protective immunity. To define antigens and epitopes of Mycobacterium tuberculosis (MTB) proteins that are presented by infected cells to CD8+ T cells, we screened 40 MTB proteins for HLA class I A*0201-binding motifs. Peptides that bound with high affinity to purified HLA molecules were subsequently analyzed for recognition by CD8+ cytotoxic T lymphocytes. We identified three epitopes recognized by CD8+ T cells from patients recovering from TB infection. Those three epitopes were derived from three different antigens: thymidylate synthase (ThyA30–38), RNA polymerase β-subunit (RpoB127–135), and a putative phosphate transport system permease protein A-1 (PstA175–83). In addition, CD8+ T cell lines specific for three peptides (ThyA30–38, PstA175–83, and 85B15–23) were generated from peripheral blood mononuclear cells of normal HLA-A*0201 donors. These CD8+ T cell lines specifically recognized MTB-infected macrophages, as demonstrated by production of IFN-γ and lysis of the infected target cells. Finally, CD8+ cytotoxic T lymphocytes reduced the viability of the intracellular MTB, providing evidence that CD8+ T cell recognition of MHC class I-restricted epitopes of these MTB antigens can contribute to effective immunity against the pathogen.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=17320Documentos Relacionados
- Suppression of virus-specific antibody production by CD8+ class I-restricted antiviral cytotoxic T cells in vivo.
- Suppression of human immunodeficiency virus type 1 replication by CD8+ cells: evidence for HLA class I-restricted triggering of cytolytic and noncytolytic mechanisms.
- Virus-specific, CD8+ major histocompatibility complex class I-restricted cytotoxic T lymphocytes in lymphocytic choriomeningitis virus-infected beta2-microglobulin-deficient mice.
- Inhibition of MHC class I-restricted antigen presentation by γ2-herpesviruses
- Major histocompatibility complex class I-restricted T cells are required for resistance to Mycobacterium tuberculosis infection.
