Immunogenomics Parameters for Patient Stratification in Alzheimer’s Disease

Abstract

Background: Despite the fact that only modest adaptive immune system related approaches to treating Alzheimer’s disease (AD) are available, an immunogenomics approach to the study of AD has not yet substantially advanced. Objective: Thus, we sought to better understand adaptive immune receptor chemical features in the AD setting. Methods: We characterized T-cell receptor alpha (TRA) complementarity determining region-3 (CDR3) physicochemical features and identified TRA CDR3 homology groups, represented by TRA recombination reads extracted from 2,665 AD-related, blood- and brain-derived exome files. Results: We found that a higher isoelectric value for the brain TRA CDR3s was associated with a higher (clinically worse) Braak stage and that a number of TRA CDR3 chemical homology groups, in particular representing bloodborne TRA CDR3s, were associated with higher or lower Braak stages. Lastly, greater chemical complementarity of both blood- and brain-derived TRA CDR3s and tau, based on a recently described CDR3-candidate antigen chemical complementarity scoring process (https://adaptivematch.com), was associated with higher Braak stages. Conclusion: Overall, the data reported here raise the questions of (a) whether progression of AD is facilitated by the adaptive immune response to tau; and (b) whether assessment of such an anti-tau immune response could potentially serve as a basis for adaptive immune receptor related, AD risk stratification?

Chemical Complementarity of Breast Cancer Resident, T-Cell Receptor CDR3 Domains and the Cancer Antigen, ARMC3, is Associated With Higher Levels of Survival and Granzyme Expression

“…The above array generations, alignments, and CS calculations were performed for every CDR3 and antigen in the input files for the adaptivematch.com web tool, which conducts the indicated mathematical manipulations. 21 , 22 Adapivematch.com processing includes the above steps for Uversky hydropathy values representing all AAs, 23 thereby providing a hydropathy CS; and performs the calculations for combination electrostatic-hydropathy CSs. To calculate the combination CS, the same sliding window CS process was repeated using both the electrostatic charge arrays and hydrophobicity arrays to generate a summed combination CS for each CDR3-candidate antigen pair.…”

Electrostatic Complementarities of Glioblastoma-Resident T-Cell Receptors and Cancer Testis Antigens Linked to Poor Outcomes and High Levels of Sphingosine Kinase-2 Expression

“…The chemical complementarity scoring is based on [ 8 ] and was facilitated by the construction of an original web tool, adaptivematch.com [ 5 , 12 , 13 ], which is publicly accessible and has been extensively benchmarked in [ 13 ]. The electrostatic complementarity scores (CSs) are generated by aligning the adaptive IR CDR3 AAs with a candidate antigen peptide sequence.…”

A Bioinformatics Assessment Indicating Better Outcomes With Breast Cancer Resident, Immunoglobulin CDR3-MMP2 Binding

“…The computer code for application of the algorithm is freely available at https://github.com/bchobrut/brca_swcs. In addition, the complementarity scoring, along with a matchup of the CSs and survival data, can be done via the publicly available adaptivematch.com (23)(24)(25), with the web tool having been specifically benchmarked in (25). The Adaptive Match web tool has instructions for use.…”