Antigen processing and T-cell responses¶
The causal chain is antigen availability → uptake or expression → generation or destruction of a core → loading and surface peptide–MHC (pMHC) → T-cell recognition and priming. Measuring a step does not measure all later steps: binding affinity does not count presented complexes, and a responding T-cell clone does not establish the amount of antigen that arrived at an APC.
Primary experiments¶
| Study | Experiment and conclusion |
|---|---|
| Manoury et al., 2002 | In human APCs processing myelin basic protein, inhibiting asparagine endopeptidase (AEP) increased presentation of the HLA-DR2 MBP(85–99) epitope; overexpressing AEP reduced it. AEP cleaves within the epitope, showing that more protease activity can destroy a target rather than generate it. |
| Bijker et al., 2008 | Compared minimal and extended OVA peptide vaccines with CpG in mice. Extended peptides yielded more sustained, dendritic-cell-focused presentation and stronger tumoricidal CTL activity; repeated minimal peptide dosing increased CTL counts without reproducing that effector quality. |
| Rosalia et al., 2013 | Compared whole protein with SLP uptake and processing in murine and human dendritic cells. SLPs reached a faster route to class-I presentation and increased CD8 activation in their in-vitro systems; protein and SLP therefore cannot share a generic processing multiplier. |
| Rabu et al., 2019 | Varied cathepsin-sensitive linkers in artificial melanoma SLPs, then tested DC presentation, donor PBMC responses and a mouse tumor model. Some linkers improved class-I clone activation by up to about 100-fold and enhanced downstream responses, while class-II effects were smaller; sequence-specific processing can alter both endpoints. |
| Influenza epitope quantification, 2019 | Quantified 21 class-I influenza ligands after direct and cross-presentation and compared them with mouse CTL responses. The immunodominant NP and PA epitopes favored different routes; pMHC abundance contributed to response magnitude together with affinity and T-cell repertoire, rather than determining it alone. |
Use in mhctools¶
The approximately 100-fold linker result is a relative concentration-response shift in one antigen, assay and APC system. It is useful as a challenge case for candidate-window ranking and to prioritize paired experiments, but it is not a transferable per-hour cut rate or a dose fraction. Likewise, prolonged in-vivo presentation after SLP vaccination includes continuing antigen input; it does not identify an intrinsic surface-pMHC half-life.
Report the stage actually assessed: protease-site score, predicted binding, measured surface pMHC, T-cell activation, or in-vivo response. The trajectory model and window comparison can propagate supplied rates and sensitivity scenarios, but their numerical output cannot be calibrated from these response studies alone. The joint calibration issue tracks the missing matched, time-resolved core-bearing fragments and APC pMHC.