Abstract:
:Bacterial antigens recognized by CD8(+) T cells in the context of MHC class I are thought to play a crucial role in protection against pathogenic intracellular bacteria. Here, we demonstrate the induction of HLA-A*0201-restricted CD8(+) T cell responses against six new high-affinity HLA-A*0201-binding CTL epitopes, encoded within an immunodominant and highly conserved antigen of Mycobacteria, the heat shock protein 65 (hsp65). One of these epitopes, Mhsp65(9(369)), is identical in a large number of pathogenic bacteria, and is recognized in a CD8-independent fashion. Mhsp65(9(369)) could be presented by either mycobacterial hsp65-pulsed target cells or BCG-infected macrophages. Interestingly, T cells specific for this epitope did not recognize the corresponding human hsp65 homologue, probably due to structural differences as revealed by modeling studies. Furthermore, in vitro proteasome digestion analyses show that, whereas the mycobacterial hsp65 epitope is efficiently generated, the human hsp65 homologue is not, thus avoiding the induction of autoreactivity. Collectively, these findings describe high-affinity HLA class I-binding epitopes that are naturally processed and are recognized efficiently by MHC class I-restricted CD8(+) T cells, providing a rational basis for the development of subunit vaccine strategies against tuberculosis and other intracellular infectious diseases.
journal_name
Eur J Immunoljournal_title
European journal of immunologyauthors
Charo J,Geluk A,Sundbäck M,Mirzai B,Diehl AD,Malmberg KJ,Achour A,Huriguchi S,van Meijgaarden KE,Drijfhout JW,Beekman N,van Veelen P,Ossendorp F,Ottenhoff TH,Kiessling Rdoi
10.1002/1521-4141(200112)31:12<3602::aid-immu3602>keywords:
subject
Has Abstractpub_date
2001-12-01 00:00:00pages
3602-11issue
12eissn
0014-2980issn
1521-4141pii
10.1002/1521-4141(200112)31:12<3602::AID-IMMU3602>journal_volume
31pub_type
杂志文章abstract::IL-10 is a potent anti-inflammatory molecule, which regulates TNF-alpha at multiple levels. We investigated whether IL-10 also modulated the activity of the TNF-alpha-converting enzyme (TACE). Using an ex vivo fluorogenic assay we observed that LPS rapidly induced TACE activity in monocytes coinciding with release of ...
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