The coordination of unprotonated peptide tertiary structure as a metric of pMHC–TCR functional avidity

Abstract

The coordination difference between the unprotonated tertiary structures of a native (Tax) peptide and a number of its variants – all peptides presented by HLA-A201 and bound to the human A6 T cell receptor-was discovered to constitute a metric of pMHC–TCR functional avidity. Moreover, increasing coordination deviations from the index were found to flag correspondingly weakening immunological outcomes of the variant peptides. The prognostic utility of the coordination difference of unprotonated tertiary structure was established to operate strictly on the peptide scale, seizing to be of relevance either to the immediate peptide environment (i.e. within the realm of peptide short range order, within 7 Å of any peptide atom) or over the entirety of the pMHC–TCR complex. Additionally, the imprint of peptide immunological identity was expressed both by the total coordination as well as by its C–C partial.

Atomic Coordination Reflects Peptide Immunogenicity

“…Previously we established that cumulative coordination difference of the protonated variant peptides in respect to the index is correlated to immunological identity (Antipas and Germenis, 2015a , b , c , d ) and, more precisely, that cumulative under-coordination is characteristic of the antagonist; at this point we inquire if this might additionally hold true for unprotonated structures and the results are shown in Figure 4 , for the cases of the isolated peptides, the cleft environment up to 7 Å from each peptide and the entire pMHC-TCR complex. Both the total PDF (Figure 4A ) and the C-C partial (Figure 4B ) were found to be correlated to peptide immunological identity (i.e., antagonist peptides were under-coordinated in respect to Tax), in agreement with our previous results of protonated structures; in contrast, he rest of the PDF partials (Figures 4C–F ) were not relevant.…”

“…Coordination refers to atomic structure and expresses the tendency of atoms to be surrounded by other atoms (the coordination number indicates the number of atoms surrounding a reference atom). The calculation of atomic coordination is based on the initial formulation of a histogram of interatomic interactions, via calculation of the distances between all atom pairs and the assignment of these distances to bins of a predefined size (e.g., 0.1 Å; choice of the most appropriate bin size is a matter of experimentation (Antipas and Germenis, 2015a , b , c , d ) but does not affect the results if chosen to be sufficiently small). By convention, the ith bin is assigned all interatomic distances, R, within the range r < R < r + Δr, where r = i * Δ r and Δr is the bin size.…”

ABD24: MHC Class I A*0201- GILGFVFTL-Vβ17Vα10.2 TCR complex: convergence diagnostics of number density

“…Analysis was based on precursor theoretical modelling related to atomic and mesoscale systems [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] .…”

ABD6: MHC Class I A*0201-LLFGYPVYV-B7 TCR complex: convergence diagnostics of number density

“…Analysis was based on precursor theoretical modelling related to atomic and mesoscale systems [1][2][3][4][5][6][7][8][9][10][11][12] .…”