![]() Second, full-length cDNA sequencing could be used to accurately determine the sequence and identity of alleles of HLA genes. Determining isoform-level transcriptomes of healthy and cancerous immune cells might inform treatment decisions and future However, evidence is accumulating that these epitopes might be absent in some isoforms expressed by these genes ( Sotillo et al. Leukemia (B-ALL) target epitopes of CD19, CD20, and CD22 ( Davila and Brentjens 2016 Fry et al. For example, current antibody and chimeric antigen receptor (CAR) T cell therapies against B cell acute lymphoblastic (1) the isoforms of surface receptors targeted in immunotherapy, (2) allele-resolved HLA transcript sequences central to self/non-self-discrimination,Īnd (3) B cell receptor (BCR) and T cell receptor (TCR) repertoires instrumental to the adaptive immune response to pathogens.įirst, full-length cDNA sequencing should be capable of investigating the transcript isoforms of surface receptors expressedīy B cells which have important roles in the immune response but are also themselves targets in the treatment of B cell–derived Accurate and deep full-length cDNA sequencing of immune cell transcriptomes could overcome this shortfall by providing However, RNA-seq, the current gold-standard for whole-transcriptome analysis, falls short of describing these immune receptorsĬompletely and accurately ( Mose et al. The transcriptsĮncoding these immune receptors are of great interest to basic and translational research as well as diagnostic and otherĬlinical purposes ( Logan et al. The human immune system relies on highly diverse and complex receptors to protect us from a wide array of pathogens. The HLA and AIRRĪnalysis approaches we introduce here are untargeted and therefore do not require prior knowledge of the composition or genetic Sequences of HLA alleles, and (3) extract detailed AIRR data for the analysis of the adaptive immune system. We used this data set to (1) show that deep and accurate full-lengthĬDNA sequencing can be used to provide isoform-level transcriptome analysis for more than 9000 loci, (2) generate accurate Generated over 10,000,000 full-length cDNA sequences at a median accuracy of 97.9% using our nanopore sequencing-based RollingĬircle Amplification to Concatemeric Consensus (R2C2) protocol. Sequencing (AIRR-seq) currently rely on our incomplete knowledge of the genetic diversity at HLA and BCR/TCR loci. Both short-read RNA-seq-based HLA typing and BCR/TCR repertoire Individual carry a vast amount of health-relevant information. In turn, the repertoires of millions of unique BCR and TCR transcripts in each In organ and bone marrow transplantations. Determining which allelesĪn individual possesses for each HLA gene (high-resolution HLA typing) is essential to establish donor–recipient compatibility These include transcriptsĮncoding human leukocyte antigen (HLA) receptors as well as B cell and T cell receptors (BCR and TCR). Together these studies further our understanding of the relationship between immune repertoire diversity and immune function.The human immune system relies on highly complex and diverse transcripts and the proteins they encode. Lastly, I explore the hypothesis that chronic cytomegalovirus infection in the elderly compromises immune function by reducing CD8+ T cell repertoire diversity. To study the diversity of the T cell repertoire in response to an acute infection, I combine live-attenuated yellow fever virus vaccination and T cell repertoire sequencing to identify and track vaccine responsive clones longitudinally. I also present two studies exploring the diversity of the T cell repertoire in acute and chronic viral infections. In this work, I present a database of B cell receptor sequences that unites experimental and computational techniques to accurately estimate the richness of the naïve and memory B cell repertoires. As a result, the diversity of B and T cell receptors in the body determine an individual's ability to respond to new and previously seen antigens. The combination of different (Variable, Diversity and Joining) gene segments, insertion and deletion of non-templated nucleotides at the junctions between segments and pairing of heavy and light chains control the specificity of recognition. The vast majority of B and T cell clones possess a single unique heterodimeric receptor with a highly diverse binding domain generated through ordered somatic gene rearrangements known as V(D)J recombination. Immunoglobulin and T cell receptors enable the immune system to recognize an enormous set of exogenous and endogenous antigens. B and T lymphocytes are the cellular effectors of the adaptive immune system and perform the learning and recall functions that are the basis of immunological memory. ![]()
0 Comments
Leave a Reply. |
Details
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |