NDLI: Evolution of the V, D, and J gene segments used in the primate γδ T-cell receptor reveals a dichotomy of conservation and diversity

Content Provider	PubMed Central
Author	Kazen, Allison R. Adams, Erin J.
Abstract	γδ T cells are an immunological enigma in that both their function in the immune response and the molecular mechanisms behind their activation remain unclear. These cells predominate in the epithelia and can be rapidly activated to provide an array of responses. However, no homologous γδ T-cell populations have been identified between humans and mice, and our understanding of what these cells recognize as ligands is limited. Here we take an alternative approach to understanding human γδ T-cell ligand recognition by studying the evolutionary forces that have shaped the V, D, and J gene segments that are used during somatic rearrangement to generate the γδ T-cell receptor. We find that distinctly different forces have shaped the γ and δ loci. The Vδ and Jδ genes are highly conserved, some even through to mouse. In contrast, the γ-locus is split: the Vγ9, Vγ10, and Vγ11 genes represent the conserved region of the Vγ gene locus whereas the remaining Vγ genes have been evolving rapidly, such that orthology throughout the primate lineage is unclear. We have also analyzed the coding versus silent substitutions between species within the V and J gene segments and find a preference for coding substitutions in the complementarity determining region loops of many of the V gene segments. Our results provide a different perspective on investigating human γδ T-cell recognition, demonstrating that diversification at particular γδ gene loci has been favored during primate evolution, suggesting adaptation of particular V domains to a changing ligand environment.
Related Links	http://dx.doi.org/10.1073/pnas.1105105108
Starting Page	332
File Format	PDF
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	29
Volume Number	108
Language	English
Publisher	National Academy of Sciences
Publisher Date	2011-07-19
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	General Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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Evolution of the V, D, and J gene segments used in the primate gammadelta T-cell receptor reveals a dichotomy of conservation and diversity.

Mechanisms that direct ordered assembly of T cell receptor β locus V, D, and J gene segments

The T cell receptor β enhancer promotes access and pairing of Dβ and Jβ gene segments during V(D)J recombination

Gene-targeted deletion and replacement mutations of the T-cell receptor beta-chain enhancer: the role of enhancer elements in controlling V(D)J recombination accessibility.

Definition of a T-Cell Receptor β Gene Core Enhancer of V(D)J Recombination by Transgenic Mapping

T-cell receptor V delta-J alpha rearrangements in human thymocytes: the role of V delta-J alpha rearrangements in T-cell receptor-delta gene deletion.

Mechanisms that direct ordered assembly of T cell receptor beta locus V, D, and J gene segments.

Germline DNA Retention in Murine and Human Rearranged T Cell Receptor Gene Coding Joints: Alternative Recombination Signal Sequences and V(D)J Recombinase Errors

Enforcement of γδ-lineage commitment by the pre–T-cell receptor in precursors with weak γδ-TCR signals

Evolution of the V, D, and J gene segments used in the primate γδ T-cell receptor reveals a dichotomy of conservation and diversity

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Evolution of the V, D, and J gene segments used in the primate gammadelta T-cell receptor reveals a dichotomy of conservation and diversity.

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