Recognition of higher order patterns in proteins: immunologic kernels.
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.
ioGenetics LLC, Madison, Wisconsin, United States of America. robert_bremel@iogenetics.com
Robert D
RD
Bremel
E Jane
EJ
Homan
D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002403:Cathepsins / Q000737:chemistry / Q000378:metabolism; D016000:Cluster Analysis; D000939:Epitopes / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D018985:Epitopes, B-Lymphocyte; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D006801:Humans; D018448:Models, Immunological; D010455:Peptides / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D011506:Proteins / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D059748:Proteolysis; D013744:Tetanus Toxin / Q000737:chemistry / Q000276:immunology / Q000378:metabolism
D000939:Epitopes; D018985:Epitopes, B-Lymphocyte; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D010455:Peptides; D011506:Proteins; D013744:Tetanus Toxin; D002403:Cathepsins