Abstract
By applying analysis of the principal components of amino acid physical properties we predicted cathepsin cleavage sites, MHC binding affinity, and probability of B-cell epitope binding of peptides in tetanus toxin and in ten diverse additional proteins. Cross-correlation of these metrics, for peptides of all possible amino acid index positions, each evaluated in the context of a ±25 amino acid flanking region, indicated that there is a strongly repetitive pattern of short peptides of approximately thirty amino acids each bounded by cathepsin cleavage sites and each comprising B-cell linear epitopes, MHC–I and MHC-II binding peptides. Such “immunologic kernel” peptides comprise all signals necessary for adaptive immunologic cognition, response and recall. The patterns described indicate a higher order spatial integration that forms a symbolic logic coordinating the adaptive immune system.
Highlights
The adaptive immune system is capable of cognition, coordinated activation, and memory recall
Our data suggests that the primary amino acid sequences of proteins contain higher order patterns combining sequence elements recognized by both stochastic and genetic components of the immune system
A coordinated, integrated response by the adaptive immune response is enabled by a form of symbolic logic, in which multiple signals or conditions are encoded together within short peptides
Summary
The adaptive immune system is capable of cognition, coordinated activation, and memory recall. It differentiates self from non-self and reacts to novel or exogenous epitopes through the integrated action of antibody and cell-mediated responses. Diverse aspects of the coordination needed to mount and recall an adaptive immune response have been described extensively in the literature over decades, among them the role of T-cell help (TH) to B-cells [1], epitope-directed processing by B-cells [2], the ability of dendritic cells to store epitope peptides and re-present them to Bcells [3,4], cross presentation by dendritic cells [5,6], and the necessity of TH cells in establishing CD8+memory [7] and to provide help for B-cell memory recall [8]. A systematic characterization of the spatial relationship of the epitope components within a protein has, been lacking
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