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“Omics” Technologies in Vaccine Research
Published in Mesut Karahan, Synthetic Peptide Vaccine Models, 2021
Vaccines provide production by means of adaptive immunity, and the innate immunity acts as an intermediate between antigens found in the vaccine and the adaptive immunity of the vaccinee. Also, identification of molecular signatures induced by vaccination is important to define the elements underlying the adaptive immune responses. Thus, the immune responses providing protection will be predicted to evaluate the potency of vaccines or to identify the unresponsive individuals. Interactions among the vaccine, innate immunity, and adaptive immunity can be investigated in detail via systems biology approaches (Buonaguro and Pulendran 2011; Petrizzo et al. 2012). It is also important to investigate the repertoire of B cell and T cell receptors needed for adaptive immune responses. The dynamic immune repertoire can be identified using high-throughput sequencing technologies via computational and systems immunology strategies (Miho et al. 2018).
Summary and Development of a New Approach to Senescence
Published in Nate F. Cardarelli, The Thymus in Health and Senescence, 2019
The thymic immune repertoire is incomplete in human beings at birth, disease protection arising in part from the presence of maternal antibodies. If neonates are given massive dosages of antigens, runting occurs. Runting is characterized by dwarfing, extreme hypoplasia of lymphoid tissue, and a shortened life-span.
Thymus Influence on Differentiation and Functional Maturation of T Lymphocytes
Published in Marek P. Dabrowski, Barbara K. Dabrowska-Bernstein, Immunoregulatory Role of Thymus, 2019
Marek P. Dabrowski, Barbara K. Dabrowska-Bernstein
To explain the apparent paradox, one can anticipate that T cells can get information on conventional antigen mediated indirectly by the self-MHC encoded surface structures presented to thymocytes inside the thymus. Supposedly, intrathymic education provides thymocytes with the memory of the “normal” shape of MHC-encoded structures, and subsequently, they are recognized by peripheral T lymphocytes as “self” and tolerated, providing the structure is identical with the one exactly memorized. In contrast, any changes in the memorized MHC-encoded structure introduced by an interaction with an antigen (vide antigen internalization, processing, and presentation by APC), while recognized by a T cell, could be responsible for an immune reaction. These reactions could be furthermore regulated by T suppressor cells. Moreover, noninfectious physicochemical agents able to interfere with self-MHC encoded structures or genetic mutations could result in a similar effect. This way of interpretation of the thymic-dependent T lymphocyte immunocompetence does not require a necessity for intrathymic spontaneous clonal mutations85 or exclusion of “forbidden clones”90 for the development of T lymphocyte immune repertoire. Instead, the hypothesis is based on a selective intrathymic or even extrathymic promotion of T lymphocyte subsets able to develop a complex of defined surface glycoprotein molecules which in concert with T cell antigenic receptor are decisive for T lymphocyte immune activity.84
Electrostatic Complementarity of T-Cell Receptor-Alpha CDR3 Domains and Mutant Amino Acids Is Associated with Better Survival Rates for Sarcomas
Published in Pediatric Hematology and Oncology, 2021
Michelle Yeagley, Boris I. Chobrutskiy, Etienne C. Gozlan, Nikhila Medikonda, Dhruv N. Patel, Shayan Falasiri, Blake M. Callahan, Taha Huda, George Blanck
Cancer immunogenomics has been approached in a number of ways. In early work, the approach was specific to isolated tumors. For example, T cell receptor (TCR) sequences facilitating the killing of a single tumor, based on specific tumor antigens, have been identified.9 More recently, bulk analyses of TILs have provided a more global or “landscape” view of cancer immunogenomics.10 Recent cancer immunogenomics has represented one of two approaches: (a) immune repertoire sequencing11; and (b) mining of exome (WXS)10,12 and RNASeq files13 for immune receptor recombination reads swept up in the production of those files, i.e., files primarily intended for mutation and gene expression analyses, respectively. While the immune repertoire approach, based on polymerase chain reaction-amplification of all, or almost all TCR recombinations present in a tumor sample, represents a clear opportunity for comprehensiveness and depth, this approach is limited in terms of the number of samples that can be assessed at any one time, essentially due to cost.
A computational method for immune repertoire mining that identifies novel binders from different clonotypes, demonstrated by identifying anti-pertussis toxoid antibodies
Published in mAbs, 2021
Eve Richardson, Jacob D. Galson, Paul Kellam, Dominic F. Kelly, Sarah E. Smith, Anne Palser, Simon Watson, Charlotte M. Deane
In antibody discovery, clonotyping is used to search for clonal relatives of lead antibodies in bulk BCR-seq data sets in order to identify antibodies that target the same epitope, but which have either an increased affinity or a superior developability profile. This process is referred to as “immune repertoire mining”. Hsiao and colleagues performed clonotyping on a set of bulk heavy-chain repertoires and used the resultant clonotypes for hit expansion against two targets.9 They achieved greater than an order of magnitude improvement in affinity for both targets and between 48% and 100% of tested heavy chain variants retained target-binding.9 This suggests that sampling within a clonotype can be highly effective as a means of repertoire mining. However, the method does not allow the identification of binders to the same epitope that derive from different clonotypes, which currently limits the sequence distinctness of novel binders that can be recovered from immune repertoires.
Current strategies for detecting functional convergence across B-cell receptor repertoires
Published in mAbs, 2021
Matthew I. J. Raybould, Anthony R. Rees, Charlotte M. Deane
In addition to prior infection/vaccination history, broader cohort characteristics can also be considered and either held constant, balanced, or varied, depending on the research question. Studies have found the immune response is dependent both on age40–42 and sex,43 and that the properties of response BCRs/antibodies depend strongly on maturation state36 (see below). Another important, yet often under-considered trait, is the geographical origin and/or ancestry of each volunteer. This is relevant since gene loci are under the influence of local environmental pressures, affecting allelic selection which in turn can play a role in disease susceptibility through different induced antibody responses.44–46 For example, IGKV2D-29*02 and IGHV3-23*03 have been found to be significantly overrepresented in North American and Asian populations respectively, correlating with differential ability to engage Haemophilus influenzae type b (Hib),46 while polymorphisms in IGHV1-69 and several IGHV2 loci have been associated with autoimmunity.47,48 A recent study has found that BCR gene recombination profiles can vary even amongst human monozygotic twins,49 so it remains unclear to what extent individual V(D)J recombination preferences can be accounted for by controlling for volunteer genetics. The role of an individual’s microbiome in shaping the nature of the baseline immune repertoire is also becoming apparent.50