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

• 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
• Journal Title: Journal of Experimental Medicine
• Volume: Volume 169, Number 1
• Publisher: Rockefeller University Press | 1989-01-01, Pages 41-57
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1084/jem.169.1.41
• Subjects: Health Sciences, Health Care Management; Health Sciences, Medicine and Surgery
• Keywords: Science & Technology; Life Sciences & Biomedicine; Immunology; Medicine, Research & Experimental; Research & Experimental Medicine; IMMUNOLOGY; MEDICINE, RESEARCH & EXPERIMENTAL

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.