Lymphocytes: Gamma Delta


γδ T cells, together with αβ T cells and B cells, are the only cells that use somatic gene rearrangement to generate diverse receptors to recognise different antigens. All three types of cells are present together in all but the most primitive vertebrates, suggesting that each type of cell functions uniquely, and all are necessary to maintain host immune competence. Indeed, γδ T cells and αβ T cells differ in antigen recognition, the generation of antigen‐specific repertoire, activation requirement and effector function development. These aspects allow γδ T cells to occupy unique temporal and functional niches in host immune defence. In infections, γδ T cells respond earlier than αβ T cells; and also emerge late after pathogen numbers start to decline. Thus, these cells may be involved in both establishing and resolving the inflammatory response.

Key Concepts

  • γδ T cells are present together with αβ T cells and B cells in all but the most primitive vertebrates. These are the only cells using somatic gene rearrangement to generate diverse receptor for antigen recognition.
  • γδ T cells contribute uniquely to host immune competence and function differently from αβ T cells in host defence and immune surveillance.
  • γδ T cells are similar to B cells in antigen recognition, in that antigens of different size, shape and molecular nature are recognised directly, and γδ T cells and B cells can recognise the same antigens.
  • γδ T cells require thymic maturation process before coming out to the periphery, and this process does very little to determine what γδ T cells can recognise, but determine how they will function.
  • γδ T cells are the major initial responders in acute infections, especially in producing IL‐17 to initiate the inflammatory response.

Keywords: T lymphocytes; antigen recognition; T‐cell activation; IL‐17; inflammation

Figure 1. Concentration of γδ TCR diversity is in the TCRδ CDR3 junction. The diversity at the murine TCRδ CDR3 junction is enhanced by (1) the presence of multiple D gene segments that can be read in all three open reading frames (ORF1–3), (2) different D regions can be joined together and (3) N‐nucleotides can be inserted into the junctions of the joining segments. Thus, despite the limited diversity at the VJ junctions of TCRγ chains, the potential diversity generated at the combined γδ CDR3 junctions (approximately 1018 combinations) is still higher than that of αβ TCRs (∼1016) and Igs (∼1011).
Figure 2. CDR3 length distributions of adaptive immune receptor chains. The CDR3 length is defined as four amino acids less than the number of amino acid residues between the J region‐encoded GXG triplet, where G is glycine and X is any amino acid, and the nearest preceding V region‐encoded cysteine. All chains were tabulated from the online Sequences of Proteins of Immunological Interest as of January 1992. Histograms show percentages of CDR3 sequences at given lengths in human chain families.
Figure 3. Modalities of self‐antigen recognition by γδ T cells. Recognition of self‐molecules by γδ T cells can be initiated/enhanced by (a) increasing surface expression such as T10/T22 on monocytes after influenza virus infection; (b) acquiring new components, either of microbial or host origin, such as the association of cardiolipin with CD1d; (c) being recruited by B7 receptor‐related molecules such as Skint‐1 or BTN3‐A1; (d) being released due to cell death, like tRNA synthetase and (e) being on infected cells, like EPCR.
Figure 4. Kinetics of T‐cell activation and T‐dependent antibody response. The development of γδ T‐cell IL‐17 response, αβ T‐cell effector (a) and T‐dependent antibody (b) responses over time is shown. After stimulation, natural γδ T cells (green) make IL‐17 within 5 h; induced antigen‐specific γδ T cells make IL‐17 within 60 h (red). Naïve αβ T cells require antigen‐specific priming, and will take at least 5–7 days to develop effector function (light green). Natural antibodies (greyish blue) produced by B1 cells are present without deliberated immune challenge. After antigen encountering, naïve B cells proliferate and differentiate and participate in either the extrafollicular response (orange), where early antibodies are made within 3–4 days, or the germinal centre response, which takes 1–3 weeks to develop (purple). γδ T cells also appear late (dark blue) and may regulate the end of the inflammatory response.

Further Reading

Y‐h C, Meyer C and Bonneville M (2014) Gamma Delta T cells: first line of defense and beyond. Annual Review of Immunology 32: 121–55.

Chien YH and Konigshofer Y (2007) Antigen recognition by gamma delta T cells. Immunological Reviews 215: 46–58.

Chothia C and Lesk AM (1987) Canonical structures for the hypervariable regions of immunoglobulins. Journal of Molecular Biology 196 (4): 901–917.

Garcia KC and Adams EJ (2005) How the T cell receptor sees antigen – a structural view. Cell 122 (3): 333–6.

Goodman T and Lefrancois L (1989) Intraepithelial lymphocytes. Anatomical site, not T cell receptor form, dictates phenotype and function. Journal of Experimental Medicine 170 (5): 1569–1581.

Gu S, Nawrocka W and Adams EJ (2015) Sensing of pyrophosphate metabolites by Vγ9Vδ2 T cells. Frontiers in Immunology 5: 688.

Haas W, Pereira P and Tonegawa S (1993) Gamma/delta cells. Annual Review of Immunology 11: 637–685.

Itohara S, Farr AG, Lafaille JJ, et al. (1990) Homing of a gamma delta thymocyte subset with homogeneous T‐cell receptors to mucosal epithelia. Nature 343 (6260): 754–757.

Jensen KD and Chien YH (2009) Thymic maturation determines gammadelta T cell function, but not their antigen specificities. Current Opinion in Immunology 21 (2): 140–5.

Raulet DH (1989) The structure, function, and molecular genetics of the gamma/delta T cell receptor. Annual Review of Immunology 7: 175–207.

Vantourout P and Hayday A (2013) Six‐of‐the‐best: unique contributions of γδ T cells to immunology. Nature Reviews Immunology 13 (2): 88–100.

Xu JL and Davis MM (2000) Diversity in the CDR3 region of V(H) is sufficient for most antibody specificities. Immunity 13 (1): 37–45.

Zinkernagel RM and Hengartner H (2001) Regulation of the immune response by antigen. Science 293 (5528): 251–253.

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How to Cite close
Chien, Yueh‐hsiu, and Chowdhury, Roshni Roy(Oct 2015) Lymphocytes: Gamma Delta. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0001195.pub3]