Relationship between tumor cell and neoantigen-specific T-cell. On one hand, tumor cells with high tumor mutational burden (TMB) produce an elevated neoantigen load. The neoantigens are processed within the tumor cell, presented by the major histocompatibility complex (MHC) molecule, and recognized by a neoantigen-specific T cell receptor (TCR). On the other hand, the TCR is represented on the T cell surface, consisting of a heterodimeric protein comprising two chains: α (TCR-α) and β (TCR-β). The highly variable complementarity determining region 3 (CDR3) of TCR-β is encoded at the gene level, in the variable (V), diversity (D), and joining (J) segments. During somatic diversification, one of each segment is randomly combined, and further diversity is introduced through insertions and/or deletions of added nucleotides. CDR3 is the main region responsible for recognizing processed antigens.