Figure 1

T-cell receptor-antigen-peptide-MHC interaction and TCR gene recombination. (a) A T-cell (pink) encountering an antigen-presenting cell (APC; blue). The APC presents peptide antigen (Ag; yellow) in complex with the larger major histocompatibility complex (MHC; turquoise). The T-cell receptor (TCR; multi-colored) binds to both the antigen and MHC, and if the binding avidity is sufficiently high the T-cell is activated. (b) A TCR heterodimer, composed of an α and β chain, engaging peptide-MHC (pMHC). Moving outward from the T cell, the constant region (green) of the TCR is anchored to the cell membrane, followed by the J region (red). In TCR α chains the J region is followed by the V region (orange), whereas in TCR β chains, a D region is located between the V and J regions. The complementarity determining region 3 (CDR3) domain, approximately 45 nucleotides long, comprises the VJ (for TCR-α) or VDJ (for TCR-β) junction. Color gradients at junctions represent the regions encoded by arbitrary, untemplated nucleotides introduced during somatic recombination, and which represent a primary source of sequence diversification and TCR variability (see (c) for details). The CDR3 regions are the main domains of the TCR that are in contact with peptide antigen, and largely determine TCR specificity. (c) Simplified representation of TCR-β VDJ gene recombination resulting in TCR diversity. The TCR-β locus is located on chromosome 7 and is approximately 620 kb in length. Initially one of the two D regions is joined with one of 13 J regions (both randomly selected), followed by joining of the DJ region to one of more than 50 V regions (also randomly selected), yielding a final VDJ region that is approximately 500 bp in length. The mechanism by which gene segments are joined also introduces base pair variability, which together with the combinatorial selection of these segments results in TCR diversity. A completely analogous process occurs for the TCR α chain, without the D gene segment included.