Atomic Coordination Reflects Peptide Immunogenicity

Abstract

We demonstrated that the immunological identity of variant peptides may be accurately predicted on the basis of atomic coordination of both unprotonated and protonated tertiary structures, provided that the structure of the native peptide (index) is known. The metric which was discovered to account for this discrimination is the coordination difference between the variant and the index; we also showed that increasing coordination difference in respect to the index was correlated to a correspondingly weakening immunological outcome of the variant. Additionally, we established that this metric quickly seizes to operate beyond the peptide scale, e.g., within a coordination shell inclusive of atoms up to a distance of 7 Å away from the peptide or over the entire pMHC-TCR complex. Analysis of molecular orbital interactions for a range of formal charges further revealed that the N-terminus of the agonists was always able to sustain a stable ammonium (NH3+) group which was consistently absent in antagonists. We deem that the presence of NH3+ constitutes a secondary observable with a biological consequence, signifying a change in T cell activation. While our analysis of protonated structures relied on the quantum chemical relaxation of the H species, the results were consistent across a wide range of peptide charge and spin polarization conditions.

Quantum Biology Research Meets Pathophysiology and Therapeutic Mechanisms: A Biomedical Perspective

“…In this perspective, there is "a cloud" of possible charge concentrations between the two peptides, at the level of sub-atomic structure, which modulates TCR degeneracy according to the specific situation and insult (for an interesting visualization of the concept, the reader is addressed to the Figure 1 of the reference Antipas et al 2015 [41]). In authors' works [41][42][43][44], statistics and quantum chemical calculations were shown to predict immunological responses.…”

“…Despite active research [111,112], there are no therapies that can directly prevent recruitment of several inflammatory cells including T cells, and the promising results obtained by targeting the adaptive immune response did not allow an optimal long-term graft survival rate [39,40,113]. If confirmed, the described work of Antipas and colleagues [41][42][43][44] on the quantum behaviour of the TCR-pMHC complex could start pioneering studies on mechanisms of actions responsible for organ rejection and for other immune dysfunctions including auto-immune diseases, where an organ is attacked by its own immune system. These studies should be deepened, with the aim of describing in detail the mechanism of action of TCR-degeneracy and TCR-pMHC complex interaction, in order to find a way to modulate it.…”

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] .…”