The quantum model of T-cell activation: Revisiting immune response theories

Abstract

Our understanding of the immune response is far from complete, missing out on more detailed explanations that could be provided by molecular insights. To bridge this gap, we introduce the quantum model of T-cell activation. This model suggests that the transfer of energy during protein phosphorylation within T cells is not a continuous flow but occurs in discrete bursts, or 'quanta', of phosphates. This quantized energy transfer is mediated by oscillating cycles of receptor phosphorylation and dephosphorylation, initiated by dynamic 'catch-slip' pulses in the peptide-major histocompatibility complex-T-cell receptor (pMHC-TcR) interactions. T-cell activation is predicated upon achieving a critical threshold of catch-slip pulses at the pMHC-TcR interface. Costimulation is relegated to a secondary role, becoming crucial only when the frequency of pMHC-TcR catch-slip pulses does not meet the necessary threshold for this quanta-based energy transfer. Therefore, our model posits that it is the quantum nature of energy transfer-not the traditional signal I or signal II-that plays the decisive role in T-cell activation. This paradigm shift highlights the importance of understanding T-cell activation through a quantum lens, offering a potentially transformative perspective on immune response regulation.

Keywords: cells; T cells; molecules; MHC; molecules; T cell receptors.

Figure 1.. The quantum model of T cell activation.

A) Polar amino acids at the interface of pMHC and the CDR3 region of the TcR cannot effectively interact when they are disoriented or when a strong bond forms (high affinity or antagonist peptides are involved). The latter does not change the conformational equilibrium, but stabilizes the inactive conformation. B) Polar amino acids at the pMHC-TcR interface repel each other while their proximity is maintained by engagement with the CD4 or CD8 coreceptors. This engagement facilitates a flipping of the CDR3 region, resulting in conformational changes in the TcR. This, in turn, allows the stretching of the T cell’s plasma membrane at the immunological synapse and subsequently lead to phosphorylation of the ITAMs. The increased energy state of the ITAMs results in the CDR3 returning to its original conformation following the transfer of energy through phosphate groups from the Zap70 to adaptor molecule LAT and Tyr192 of LcK, autophosphorylation of LcK at Tyr 505, dissociation of Zap70 from ITAMs, allowing dephosphorylation of ITAMs by CD45. This process of repeated phosphorylation and dephosphorylation of the ITAMs ultimately triggers T cell activation through a sequence of catch and slip bonds.

Figure 2.. Diversity of CDR3 sequences in a single T cell.

Different CDR3 sequences generate through nucleotide deletion and insertion during V(D)J recombination are shown as red, green and blue color lines on each TcRβ.