A DR17-restricted T cell epitope from a secreted Mycobacterium tuberculosis antigen only binds to DR17 molecules at neutral pH
✍ Scribed by Annemieke Geluk; Krista E. Van Meijgaarden; Rene R. P. De Vries; Alessandro Sette; Tom H. M. Ottenhoff
- Book ID
- 102827457
- Publisher
- John Wiley and Sons
- Year
- 1997
- Tongue
- English
- Weight
- 592 KB
- Volume
- 27
- Category
- Article
- ISSN
- 0014-2980
No coin nor oath required. For personal study only.
✦ Synopsis
A DR17-restricted T cell epitope from a secreted Mycobacterium tuberculosis antigen only binds to DR17 molecules at neutral pH
The assembly of peptide-major histocompatability class I1 complexes in vitro is accelerated at low pH, comparable to that found in the intracellular compartments of metabolically active antigen-presenting cells (APC). Mycobacteria such as Mycobacterium tuberculosis reside in phagosomes with only mildly acidic pH. Therefore, we investigated the pH dependency of peptide-HLA-DR binding for several T cell epitopes of mycobacterial proteins, focussing particularly on well-defined, immunodominant HLA-DR17(3)-restricted Tcell epitopes: peptide (p) 3-13 from the cytoplasmic 65-kDa heat shock protein of M. tubercu-losislM. leprae, and peptide 56-65 from the secreted 30/31-kDa protein from M. tuberculosislM. leprae. p3-13 bound to purified, cell-free DR17 under both acidic and neutral conditions. Four other, unrelated DR17-binding peptides showed the same pH-dependent binding characteristics as p3-13. p56-65, however, only bound to purified DR17 at pH 7 but not at all at pH 4.5. These DR17 peptide binding data were confirmed in cell-bound DR17, in Tcell stimulation assays in which fixed APC were peptide-pulsed at acidic or neutral pH before addition of peptide-specific DR17-restricted Tcells. As far as we are aware, p56-65 is the only human Tcell epitope binding to HLA exclusively at neutral pH. The binding characteristics of p56-65 may reflect dominant processing in alternative, less acidic vacuolar compartments specifically related to the generation of epitopes from (secreted) mycobacterial proteins. The observation that p56-65 is an immunodominant epitope for anti-mycobacterial T cells suggests the relevance of such novel processing compartments in T cell-mediated immunity.