Phosphorylated peptides are naturally processed and presented by major histocompatibility complex class I molecules in vivo - PubMed (original) (raw)
Phosphorylated peptides are naturally processed and presented by major histocompatibility complex class I molecules in vivo
A L Zarling et al. J Exp Med. 2000.
Abstract
Posttranslational modification of peptide antigens has been shown to alter the ability of T cells to recognize major histocompatibility complex (MHC) class I-restricted peptides. However, the existence and origin of naturally processed phosphorylated peptides presented by MHC class I molecules have not been explored. By using mass spectrometry, significant numbers of naturally processed phosphorylated peptides were detected in association with several human MHC class I molecules. In addition, CD8(+) T cells could be generated that specifically recognized a phosphorylated epitope. Thus, phosphorylated peptides are part of the repertoire of antigens available for recognition by T cells in vivo.
Figures
Figure 1
MS/MS spectrum of the HLA-A*0201–associated peptide RLDpSYVRSL. Predicted masses for the ions of type b and y are shown above and below the sequence, respectively. Those observed are underlined. ▵, loss of phosphoric acid from the corresponding ion of type b or y.
Figure 2
Discrimination of phosphorylated peptides by CD8+ T lymphocytes. (A) IFN-γ production by phosphopeptide-specific CD8+ T cells. CD8+ T cells (generated by long-term culture with the indicated peptides as described in Materials and Methods) were stimulated for 5 h with CIR-AAD that had been pulsed with 25 μM of one of the indicated phosphorylated peptides and then assayed for the intracellular accumulation of IFN-γ. Nonspecific IFN-γ accumulation was determined by the stimulation of CD8+ T cells with unpulsed CIR-AAD and was <100/105 CD8+ T cells. (B) Specificity of GLDpSYVRSL-specific CTLs. CD8+ T cells elicited by stimulation with 1 μM GLDpSYVRSL were analyzed for cytolytic activity using 51Cr-labeled CIR-AAD targets (E/T ratio of 3:1) that had been pulsed with the indicated concentrations of phosphorylated GLDpSYVRSL, RLDpSYVRSL, GLDpYYVRSL, and GLDpTYVRSL, or nonphosphorylated GLDSYVRSL. Specific lysis of unpulsed CIR-AAD targets was <2%.
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