Crossrecognition by CD8 T cell receptor αβ cytotoxic T lymphocytes of peptides in the self and the mycobacterial hsp60 which share intermediate sequence homology
✍ Scribed by Ulrich Zügel; Bernd Schoel; Shigeki Yamamoto; Hartmut Hengel; Bror Morein; Stefan H. E. Kaufmann
- Publisher
- John Wiley and Sons
- Year
- 1995
- Tongue
- English
- Weight
- 927 KB
- Volume
- 25
- Category
- Article
- ISSN
- 0014-2980
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✦ Synopsis
Crossrecognition by CD8 T cell receptor ap cytotoxic T lymphocytes of peptides in the self and the mycobacterial hsp60 which share intermediate sequence homology* Immunization of C57BL/6 mice with the mycobacterial heat shock protein (hsp) 60 in immunostimulating complexes caused the in vivo activation of autoreactive major histocompatibility complex class I (H-2Db)-restricted CD8 T cell receptor (TcR) a@ cells. A CD8 TcR a@ clone with specificity for the mycobacterial hsp60 peptide499-508 was derived from this immunization, which, in addition, recognized syngeneic macrophages which had been stressed by interferon-y (IFN-y) stimulation. The stress-induced, self peptide could be extracted from IFN-ystressed macrophages by acid elution, suggesting that the IFN-y-induced self peptide is derived from an endogenous protein. Based on our observation that lysis of stressed target cells by this cytotoxic T lymphocyte (CTL) clone was specifically inhibited by hsp60-specific antisense oligonucleotides, we used synthetic peptides representing amino acid (aa) sequences of the murine hsp60 for target cell sensitization and identification of the relevant self peptide. Synthetic peptides representing 9-mer to 11-mer aa sequences of the murine hsp60 with asparagine in anchor position 4 or 5 as the minimal requirement for H-2Db binding were tested in CTL assays. The overlapping murine hsp60 peptides162-1701171 were stimulatory at a concentration as low as 10-100 pM. Seven other peptides of the murine hsp60 required intermediate peptide concentrations of 10-100nM for recognition by the CTL clone. Although the murine and mycobacterial hsp60 peptides recognized by this CTL clone showed only intermediate homology (3 identical and 3 similar aa), our data suggest that endogenous hsp60 itself is the source of self peptide(s) presented by IFN-ystressed macrophages to the cross-reactive CTL clone with promiscuous specificity. This notion is consistent with the idea of hsp as a link between infection and autoimmunity.