Antigen Recognition by T Lymphocytes

Abstract

T lymphocytes (or T cells) are thymus‐derived and are key players in the adaptive cellular immunity. They recognize antigen by means of their T‐cell receptor (TCR), which consist of two chains, and are surface expressed upon association with invariant CD3 units, which mediate TCR signalling. TCR, especially αβ TCR, exhibit a vast diversity, provided by the somatic rearrangement of TCR gene segments. γδ and αβ T cells exhibit important differences regarding tissue localization and antigen recognition. αβ T cells express as coreceptor CD4 or CD8. CD4+ T cells are MHC class II‐restricted and comprise T helper (TH) and regulatory (Treg) T cells. CD8αβ+ T cells are MHC class I‐restricted and are predominantly cytotoxic T cells (CTL). γδ T cells constitute as a link between innate and adaptive immunity. They are found frequently in epithelia (e.g. skin and intestine) and recognize nonclassical MHC class Ib molecules and diverse small nonpeptidic compounds in a coreceptor and MHC restriction independent manner.

Keywords: TCR; MHC; CD8; CD4; T‐cell activation; antigen recognition

Figure 1.

Binding of pMHC to TCR and coreceptor. (a, d) cartoons showing the binding of pMHC class I (a) or MHC class II (d) on an APC to TCR and CD8 (a) or CD4 (d) on a T cell. (b,c) Kb‐dEV8 peptide in complex with the 2C TCR and mCD8αα in front (b) and in side view (c). (e, f) Structure of DR4‐HA 306‐316 peptide in complex with the 1.7 TCR and D1 and D2 of CD4 in front (e) or side view (f). The MHC is in orange, the peptide in green, the TCRα chain violet, TCRβ chain grey, CD8αα in dark blue (upper unit) and light blue (lower unit). CD8αα was introduced in the Kb‐dEV8‐2C TCR complex by superimposing its Kb with Kb from the Kb‐CD8αα complex. D1 and D2 of CD4, shown in blue, were introduced by superimposition of the MHC α‐carbons of the DR4‐HA 306‐316‐1.7 TCR and the hCD4‐I‐Ak complexes.

Figure 2.

αβ TCR structure and function. (a) The assembly of CD3 with TCR. (from Call et al., ). (b) Model of a TCR/CD3 complex and CD8 on a CTL binding to a pMHC complex on a target cell. TCR is in green, CD3δ in cyan, CD3γ in grey‐brown, CD3ɛ in blue, MHC in blue, peptide in red and CD8 in brown and yellow. (from Rudolph et al., ). (c) Model of a TCR‐pMHC–CD8 complex including the N and O‐linked glycans (shown in brown) (from Rudd et al., 2001). (d) TCR signaling: a triggered TCR (yellow) binds to MHC (light blue) – peptide (red) complex on a target cell. Co‐engagement by CD8 (dark blue) brings activated lck (blue) close to CD3 (orange), thus promoting phosphorylation of their ITAMs (green), resulting in the recruitment and activation of ZAP‐70 (cyan), which in turn phosphorylates LAT (violet) and SLP‐76 (light green).

Figure 3.

Models of TCR triggering. (a) Pseudo dimer model according to which CD4 crosslinks TCR by associating with one and binding to a pMHC engaging another (see Krogsgaard et al., ). (b) Kb‐dEV8–2C TCR and mCD8αα dimer in side (left) and top view (right). (c) Linear polymer of Kb‐dEV8–2C TCR and mCD8αα dimers. The same colour codes are used as in Figure . The red dots indicate the MHC α3 C‐termini.

Figure 4.

(a) Structure of the G8 γδ TCR in complex with T22. For colour code see Figure . (b) Thymic differentiation of γδ T cells before (E) and after birth. (c) Programmed expression of Vγ chains in the mouse thymus. (d) Morphology of DETCs.

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References

Adams EJ, Chien YH and Garcia KC (2005) Structure of a γδ T cell receptor in complex with the non‐classical MHC T22. Science 308: 227–231.

Arcaro A, Gregoire C, Bakker T et al. (2001) CD8β endows CD8 with efficient coreceptor function by coupling TCR/CD3 to raft‐associated CD8/p56lck complexes. Journal of Experimental Medicine 194: 1485–1495.

Bacchetta R, Gregori S and Roncarolo MG (2005) CD4+ regulatory T cells: mechanisms of induction and effector function. Autoimmunity Reviews 4: 491–496.

Call ME, Pyrdol J, Weidmann M and Wucherpfennig KW (2002) The organizing principle in the formation of the T cell receptor–CD3 complex. Cell 111: 967–979.

Call ME and Wucherpfennig KW (2005) The T cell receptor: critical role of the membrane environment in receptor assembly and function. Annual Review of Immunology 23: 101–125.

Cebecauer M, Guillaume P, Mark S et al. (2005) CD8+ Cytotoxic T lymphocyte activation by soluble major histocompatibility complex (MHC)‐peptide dimers. Journal of Biological Chemistry 280: 23820–23825.

ChienYH and Bonneville M (2006) Gamma delta T cell receptors. Cellular and Molecular Life Sciences 63: 2089–2094.

Cochran JR, Cameron TO, Stone JD, Lubetsky JB and Stern LJ (2001) Receptor proximity, not intermolecular orientation, is critical for triggering T‐cell activation. Journal of Biological Chemistry 276: 28068–28074.

Comelli EM, Sutton‐Smith M, Yan Q et al. (2006) Activation of murine CD4+ and CD8+ T lymphocytes leads to dramatic remodeling of N‐linked glycans. Journal of Immunology 177: 2431–2440.

Dong C and Flavell RA (2001) TH1 and TH2 cells. Current Opinion in Hematology 8: 47–51.

Ferrero I, Wilson A, Beermann F, Held W and MacDonald HR (2001) T cell receptor specificity is critical for the development of epidermal γδ T cells. Journal of Experimental Medicine 194: 1473–1483.

Garcia KC, Degano M, Stanfield RL et al. (1996) An αβT cell receptor structure at 2.5 Å and its orientation in the TCR–MHC complex. Science 274: 209–219.

Garboczi DN, Ghosh P, Utz U et al. (1996) Structure of the complex between human T‐cell receptor, viral peptide and HLA‐A2. Nature 384: 134–141.

Hayes SM and Love PE (2002) Distinct structure and signaling potential of the γδ TCR complex. Immunity 16: 827–838.

Irvine DJ, Purbhoo MA, Krogsgaard M and Davis MM (2002) Direct observation of ligand recognition by T cells. Nature 419: 845–849.

Kane LP, Lin J and Weiss A (2000) Signal transduction by the TCR for antigen. Current Opinion in Immunology 12: 242–249.

Krogsgaard M, Li QJ, Sumen C et al. (2005) Agonist/endogenous peptide‐MHC heterodimers drive T cell activation and sensitivity. Nature 434: 238–243.

Luescher IF, Vivier E, Layer A et al. (1995) CD8 modulation of T‐cell antigen receptor‐ligand interactions on living cytotoxic T lymphocytes. Nature 373: 353–356.

Maekawa A, Schmidt B, Fazekas de St Groth B, Sanejouand YH and Hogg PJ (2006) Evidence for a domain‐swapped CD4 dimer as the coreceptor for binding to class II MHC. Journal of Immunology 176: 6873–6878.

Minguet S, Swamy M, Alarcon B, Luescher IF and Schamel WW (2007) Full activation of the T cell receptor requires both clustering and conformational changes at CD3. Immunity 26: 43–54.

Moody AM, Chui D, Reche PA et al. (2001) Developmentally regulated glycosylation of the CD8αβ coreceptor stalk modulates ligand binding. Cell 107: 501–512.

Randolph DA and Fathman CG (2006) Cd4+Cd25+ regulatory T cells and their therapeutic potential. Annual Review of Medicine 57: 381–402.

Reinhardt RL, Kang SJ, Liang HE and Locksley RM (2006) T helper cell effector fates – who, how and where? Current Opinion in Immunology 18: 271–277.

Roncarolo MG, Gregori S, Battaglia M et al. (2006) Interleukin‐10‐secreting type 1 regulatory T cells in rodents and humans. Immunological Reviews 212: 28–50.

Rudolph MG, Stanfield RL and Wilson IA (2006) How TCRs bind MHCs, peptides, and coreceptors. Annual Review of Immunology 24: 419–466.

Tato CM, Laurence A and O'Shea JJ (2006) Helper T cell differentiation enters a new era: le roi est mort; vive le roi! Journal of Experimental Medicine 203: 809–812.

Wulfing C, Sumen C, Sjaastad MD et al. (2002) Costimulation and endogenous MHC ligands contribute to T cell recognition. Nature Immunology 3: 42–47.

Yamasaki S, Ishikawa E, Sakuma M et al. (2006) Mechanistic basis of pre‐T cell receptor‐mediated autonomous signaling critical for thymocyte development. Nature Immunology 7: 67–75.

Yamazaki S, Inaba K, Tarbell KV and Steinman RM (2006) Dendritic cells expand antigen‐specific Foxp3+ CD25+ CD4+ regulatory T cells including suppressors of alloreactivity. Immunological Reviews 212: 314–329.

Yokosuka T, Sakata‐Sogawa K, Kobayashi W et al. (2005) Newly generated T cell receptor microclusters initiate and sustain T cell activation by recruitment of Zap70 and SLP‐76. Nature Immunology 12: 1253–1262.

Further Reading

Castellino F and Germain RN (2006) Cooperation between CD4+ and CD8+ cells: when, where and how. Annual Review of Immunology 24: 519–540.

Hayday AC (2000) T cells: a right time and a right place for a conserved third way of protection. Annual Review of Immunology 18: 975–1026.

Mescher MF, Curtsinger JM, Agarwal P et al. (2006) Signals required for programming effector and memory development by CD8+ T cells. Immunological Reviews 211: 81–92.

Thedrez A, Sabourin C, Gertner J et al. (2007) Self/non‐self discrimination by human T cells: simple solutions for a complex issue? Immunological Reviews 215: 123–135.

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Ferrero, Isabel, Michelin, Olivier, and Luescher, Immanuel(Sep 2007) Antigen Recognition by T Lymphocytes. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001229.pub2]