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A Peptide Filtering Relation Quantifies MHC Class I Peptide Optimization

Figure 6

Peptide optimization and trafficking for H2−K.

The model of Fig. 2 was calibrated for H2− by varying the rates of peptide binding, MHC degradation at the cell surface, and egress (Table S2 in Text S1; Protocol S2). Each simulation computes the steady state of the model with three types of peptide: two background peptides and and one of the four SIINFEKL peptide variants ( estimated from data in panel A). (A) Release of peptides from MHC following treatment with brefeldin A (BFA) measured with 25.D1 (symbols), fitted to single exponential decays (solid lines). (B) Dissociation of endogenous peptides from cells treated with BFA. (C) Steady-state presentation of specific peptide-MHC complexes at the cell surface, comparing simulation with measurements of 25.D1 from [5]. (D) Total steady-state peptide-MHC complexes (cell surface), comparing simulation with measurements of Y3 from [5]. Simulated values were scaled by a proportionality factor for optimally overlapping the 25.D1 data (with SIINFEKM removed) and the Y3 data (all points) (Text S1). (B–D) The x-axis shows the relative affinity of peptides given by the inverse of the off-rate. Steady state concentrations were obtained by equating the right hand sides of the ODEs to zero. Steady state concentrations in tapasin-deficient cells were simulated by setting . (E–G) For quantifying egression of peptide-MHC complexes, .220. (E) and .220..Tpn (F) were pulsed for 10 min with -Met/Cys and chased for the indicated times (min). Y3 immunoprecipitates were digested with endoglycosidase-H (EndoH) and SDS-PAGE and autoradiography were performed. Arrows indicate heavy chain resistant (R) and sensitive (S) to EndoH digestion. EndoH analysis of H2− was performed as described previously [6]. (B–D, G) The solid lines indicate model simulations and triangles indicate measured data-points. The experimental data for (A,B,E–F) is novel, while the experimental data for (C,D) is from [5].

doi: https://doi.org/10.1371/journal.pcbi.1002144.g006