The adaptive immune system is an essential part of the vertebrate immune system. It is a necessary system to produce specific antibodies against antigen invasion and has a memory function. The system includes T cells and B cells, which provide different antibodies based on different antigenic structures to prevent pathogens and antigens from entering basal cells. The recognition of an antigen depends on the receptors on the surface of the immune cells, i.e. T cell receptors(TCR) or B cell receptors(BCR). When the antigen is recognized, T cells will clone in large numbers and promote B cells to secrete the specific antibodies to neutralize the antigen molecules.
TCR is a heterodimer composed of two chains TRA and TRB [2, 3]. Depending on the diversity caused by the different constituent chains of TCR, T cells can be divided into αβT cells and γδT cells . Among them, αβT cells mainly involve in cellular immunity. γδT cells mainly distribute in the mucosa and skin immune system, which can directly recognize specific antigens and kill target cells. Here we only discuss the TCR produced by αβT cells. BCR, which is distributed on the surface of B cell membrane, is a tetramer with two heavy chains (H chain) and two light chains (L chain) connected by two disulfide bonds. The epitope on the surface of the antigen molecule can be accurately recognized by and bound explicitly to BCR, thereby the humoral immunity arise.
The structures of TCR and BCR chains include V, J and CDR3 regions. The V region is the most diverse species relative to other regions and is one of the primary sources of receptor diversity. It including two complete complementarity-determining areas (CDR1 and CDR2) and a portion of CDR3, is variable in TCR and BCR. The J region is a junction region in TCR and BCR. The type of J region is also an essential factor in the variety of TCR and BCR. The CDR3 area is the region connecting the V gene and the J gene. CDR3 integrates all nucleotide insertions or deletions during gene recombination and is the region with the most mutations. Therefore, analyzing the sequence of the CDR3 region is very important for studying the characteristics of TCR and BCR.
The more types of TCR and BCR clones and the higher diversity of T cells and B cells, the more active the immune system becomes. The diversity mainly stems from four mechanisms[10, 11]: combinations of different VDJ gene fragments; the random insertion and deletion of different gene segments; combinations of different heavy and light chains; and unique random high-frequency mutations to the receptor of B cells. It has been estimated that these mechanisms could cause thousands of different B-cell and T-cell receptors. The diversity of TCR and BCR can be stimulated by different antigens and has specificity for antigen. For a particular infection or disease, T cells and B cells in the immune system respond and produce specific TCR and BCR sequences for the antigen. Thus a particular receptor sequence has the potential to be a marker of a specific virus, bacterium, or fungus[14, 15].
Common methods for detecting receptor sequences include flow cytometry, PCR[17, 18], and immune repertoires sequencing[19, 20]. In recent years, RNA-seq analysis gradually becomes a new technology to avoid the limitations of these methods. RNA-seq technology can provide important biological informations so as to reveal biomarkers for the diagnosis, monitoring, and treatment of diseases[21, 22].In recent years, the studies on the diversity of TCR and the use of TCR-modified T cells for immunotherapy based on RNA-seq technology continue rising. The association of TCR diversity with MHC class II expression in tumour tissue and the public T cells enrichment in the tumour environment has been examined in the literature. Some studies also reported the relationships between the diversity and clonality of TCR and certain diseases, such as DCI and some cancer types, and proposed several identification methods based on TCR specific analysis. In addition, the use of TCR to treat diseases has also made great progress. Jakobsen used high-affinity TCR modified T cells to treat patients with melanoma, in which 55% patients showed clinical responses. Therefore, discussing the TCR and BCR sequences in pan-cancer in a more comprehensive manner is meaningful for developing tumour immunotherapy. Based on the aforementioned advantages of RNA-seq technology and the importance of TCR and BCR diversity, we collected the RNA-seq data of four types of cancers and fully described their immune repertoires, including the clone diversity and the sequences features, in order to find out the TCR and BCR characters with tumour specificity.