Development of a new monoclonal antibody specific to mouse Vγ6 chain

Abstract

There are seven Vγ gene segments in the TCR γ chain loci of mice. We developed monoclonal antibodies (mAbs) specific to the Vγ6 chain (Heilig & Tonegawa nomenclature). By immunizing Vγ4/6 KO mice with complementarity-determining region peptides in Vγ6 chains, we generated three hybridomas. These hybridomas produced mAbs capable of cell surface staining of Vγ6/Vδ1 gene–transfected T-cell line lacking TCR as well as of Vγ1− Vγ4− Vγ5− Vγ7− γδ T cells and the CD3high TCRδint γδ T cells in various organs. The location of Vγ6+ γδ T cells, which peaked in the newborn thymus, was associated with mTEC. In vivo administration of clone 1C10-1F7 mAb impaired protection against Klebsiella pneumoniae infection but ameliorated psoriasis-like dermatitis induced by imiquimod treatment. These new mAbs are useful to elucidate the development, location, and functions of Vγ6 γδ T cells in mice.

Innate Lymphocytes in Psoriasis

“…Importantly, TCRδ −/− mice reconstituted with Vγ4 and Vγ6 subpopulations restored disease susceptibility (18). Similarly, selective depletion of Vγ6 + or Vγ4 + γδ T cells using antibody-mediated or genetic depletion approaches indicate that both subsets are necessary and sufficient for IMQ-induced inflammation (38,39). Interestingly, Vγ4 + γδ T cells have been shown to have memory-like capacity.…”

Gut γδ T cells as guardians, disruptors, and instigators of cancer

“…10,13 After Vγ5 cells, Vγ6 cells start to expand from E16 in mice followed by Vγ4 and Vγ1 cells. 10,11,14,15 Recently, a monoclonal antibody specific for Vγ6 chain was developed, which has allowed the acquisition of more specific information about Vγ6 cell development. 15 Vγ6 cells arise in the fetal thymus, like other subpopulations.…”

“…10,11,14,15 Recently, a monoclonal antibody specific for Vγ6 chain was developed, which has allowed the acquisition of more specific information about Vγ6 cell development. 15 Vγ6 cells arise in the fetal thymus, like other subpopulations. Their numbers (together with Vγ5 cells) start diminishing after birth, while Vγ1 and Vγ4 cells continue to expand.…”

“…Their numbers (together with Vγ5 cells) start diminishing after birth, while Vγ1 and Vγ4 cells continue to expand. 15 Vγ5 cells, which express an invariant TCR chain, then migrate to the skin, proliferate within the skin, and exist there for their entire life as dendritic epidermal T cells (DETCs). 16 Vγ6 cells also express a semi-invariant TCR, 17,18 and these cells localize primarily to reproductive organs, tongue, and lung.…”

“…They exist mostly as self-generating, tissue-resident cells. 15,[22][23][24][25][26] The development of Vγ1 and Vγ4 cells in the thymus continues throughout adult life, where these cells emerge in a naive state, similar to αβ T cells. Vγ1 and Vγ4 cells travel throughout the body, and they are enriched in secondary lymphoid organs.…”