T-cell Receptors

Antigen recognition by T lymphocytes is achieved via / or / T-cell receptors, which are both produced through somatic rearrangement of gene segments. Upon their engagement by antigens, T-cell receptors trigger a complex sequence of events that ultimately lead to T-cell activation.

Keywords: T lymphocyte; gene recombination; antigen; TCR /; TCR /

Figure 1. Overall structure of the T cell antigen recognition complex. (a) Overall structure of pre-TCR and TCR. See text for details. (b) Assembly of the TCR/CD3 complex. Dotted lines represent interactions between the two acidic residues located within the TM region of CD3 dimers and one basic residue (either arginine in red or lysine in dark blue) located in the TM region of TCR and chains. ITAMs are represented as grey ovals in the intracytoplasmic region of CD3 subunits. See text for further details.
Figure 2. Rearrangement of TCR V(D)J elements through recognition of recombination signal sequences (RSS). Schematic representation of an RSS with consensus heptamer and nonamer sequences (top), and of TCR VJ or VDJ rearrangements according to the 12/23 rule (see text for details).
Figure 3. Genomic organization of the TCR loci. Schematic representation of VDJ segments (grey rectangles), promoters (arrows) and enhancers (coloured circles) in human TCR loci. Regions under control of a given enhancer or promoter are represented as coloured lines (when known). See text for details.
Figure 4. Intrathymic T-cell differentiation and TCR repertoire selection. Thymocyte differentiation stages are defined by expression of combination of differentiation markers (CD44, CD25), CD4/CD8 coreceptors and either pre-TCR or TCR. The two major developmental checkpoints ( and selection) are represented by arrows. Expression of recombinases and ongoing V(D)J rearrangements along thymocyte maturation are represented as red and blue rectangles, respectively. See text for details.
Figure 5. Crystallographic analysis of an TCR and an TCR/pMHC complex. (a) Structure of a murine TCR (TCR 2C, PDB access code 1tcr). (b) Structure of a TCR/pMHC class I complex (KB5-C20 H-2Kb, PDB access code 1kj2) (left) and of a TCR/pMHC II complex (HA1.7 HLA-DR1, PDB access code 1fyt) (right). CDR1 in green, CDR2 in red, CDR3 in blue, CDR3 in cyan, CDR4 in purple. Antigenic peptide residues : anchor motifs in cyan, residues pointing towards the TCR in gold, residues outside the MHC groove (for MHC class II only) in grey. Atoms : nitrogen in blue, oxygen in red. See text for details. (Courtesy of D. Housset, Grenoble, France).
Figure 6. Schematic representation of an immunological synapse. See text for details.
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 References
    Allison TJ, Winter CC, Fournié JJ, Bonneville M and Garboczi DN (2001) Structure of a human T cell antigen receptor. Nature 411: 820–824.
    Arstila TP, Casrouge A, Baron V et al. (1999) A direct estimate of the human alphabeta T cell receptor diversity. Science 286: 958–961.
    Call ME, Pyrdol J, Wiedmann M and Wucherpfennig KW (2002) The organizing principle in the formation of the T cell receptor-CD3 complex. Cell 111: 967–979.
    Crowley MP, Fahrer AM, Baumgarth N et al. (2000) A population of murine gamma/delta T cells that recognize an inducible MHC class Ib molecule. Science 287: 314–316.
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 Further Reading
    Call ME and Wucherpfennig KW (2004) Molecular mechanisms for the assembly of the T cell receptor–CD3 complex. Molecular Immunology 40: 1295–1305.
    Holler PD and Kranz DM (2003) T cell receptors: affinities, cross-reactivities and a conformer model. Molecular Immunology 40: 1027–1031.
    Housset D and Malissen B (2003) What do TCR-pMHC crystal structures teach us about MHC restriction and alloreactivity? Trends in Immunology 24: 429–437.
    Huppa JB and Davis M (2003) T cell antigen recognition and the immunological synapse. Nature Reviews in Immunology 3: 973–983.
    Krangel MS (2003) Gene segment selection in V(D)J recombination: accessibility and beyond. Nature Immunology 4: 624–630.
    Rudolph MG and Wilson IA (2002) The specificity of TCR/pMHC interaction. Current Opinion in Immunology 14: 52–65.
    Sebzda E, Mariathasan S, Ohteki T et al. (1999) Selection of the T cell repertoire. Annual Reviews in Immunology 17: 829–874.
    Von Boehmer H and Fehling HJ (1997) Structure and function of the pre-T cell receptor. Annual Reviews in Immunology 15: 433–452.
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How to Cite close
Bonneville, Marc, and Saulquin, Xavier(Sep 2005) T-cell Receptors. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0000915]