Diversity And Organization Of Human T-Cell Receptor-Delta Variable Gene Segments

• Type of Material: Article
• Authors: Shingo Hata, Harvard University; Martha Clabby, Emory University; Peter Devlin, Harvard University; Hergen Spits, Unicet Laboratory for Immunological Research; Jan E. De Vries, Unicet Laboratory for Immunological Research; Michael S. Krangel, Harvard University
• Language: English
• Date: 1989-01-01
• Publisher: Rockefeller University Press
• Publication Version: Final Published Version
• Copyright Statement: m The Rockefeller University Press
• Final Published Version (URL): http://dx.doi.org/10.1084/jem.169.1.41
• Title of Journal or Parent Work: Journal of Experimental Medicine
• ISSN: 0022-1007
• Volume: 169
• Issue: 1
• Start Page: 41
• End Page: 57
• Grant/Funding Information: This work was supported by grant DCB-8617540 from the National Science Foundation.
• Keywords: MEDICINE, RESEARCH & EXPERIMENTAL; IMMUNOLOGY; Research & Experimental Medicine; Life Sciences & Biomedicine; Medicine, Research & Experimental; Immunology; Science & Technology
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Health Care Management

Abstract

Previous studies of the human TCR-δ gene identified a single commonly used V(δ) segment, denoted V(δ)1. To better understand the extent of the human TCR-δ V gene repertoire, TCR-δ transcripts and gene rearrangements were examined in a new panel of cloned human TCR-γ/δ lymphocytes. Through this analysis we identified and determined the structures of two new V(δ) segments, denoted V(δ)2 and V(δ)3. These V(δ) segments are different from previously characterized V(α) segments, supporting the notion that the human V(δ) and V(α) repertoires are distinct. Examination of V(γ) gene segment usage in these cells reveals that the V(δ)2 gene segment is used in conjunction with the V(γ)2 gene segment. Blot hybridization indicates that the V(δ)2 gene segment lies between V(δ)1 and D(δ)-J(δ)-C(δ), and within 100 kb of the latter. Analysis of genomic clones indicates that the V(δ)3 gene segment lies in an inverted orientation, ~2 kb 3' of C(δ). This implies that rearrangement of V(δ)3 to D(δ)-J(δ)-C(δ) occurs by inversion. Together with previous mapping studies, these results indicate that human V(δ) segments are dispersed, rather than clustered, within the TCR-α/δ locus. The analysis of rearrangements in polyclonal thymocyte DNA suggests that there may be a limited number of additional V(δ) gene segments yet to be characterized.