T cell receptor V beta gene usage in a human alloreactive response. Shared structural features among HLA-B27-specific T cell clones.

Abstract

A strategy, based on using V beta family-specific oligonucleotides, was developed for specific amplification and direct sequencing of human TCR V beta genes. With this strategy, it was possible to undertake a structural analysis of TCRs from human T cell clones in specific responses. 12 HLA-B27-specific cytotoxic clones were examined. The results reveal a nonrandom use of V beta gene diversity in this alloreactive response in that: (a) the clones express a restricted number of V beta segments, including a subset of V beta families that are significantly more related to one another than to most other V beta families; (b) five of seven clones having a particular reaction pattern with HLA-B27 subtypes possess Alanine at the D-J junction; and (c) identical J beta segments are found associated in several instances with identical or highly homologous V beta gene segments. In addition, two new V beta 13 members are reported.

A New Window into the Human Alloresponse

“…48–50 Spectratyping, which examined distribution of CDR3 lengths within each V-Jβ family 51 , suggested the activation of many TCRs, with a near-Gaussian distribution among multiple Vβ families in human and rat cells responding in MLRs, 52 consistent with previous studies focusing on smaller, more targeted alloreactive populations 53 . Thus, it was surmised that the alloreactive repertoire is highly diverse.…”

Restricted V? gene usage of tumour-infiltrating T lymphocytes in primary gastric malignant B-cell lymphoma

“…Increasing numbers of studies have reported on restricted TCR ~ usage in various diseases, such as experimental allergic encephalomyelitis [1,42], allograft rejection [6,23], multiple sclerosis [29], Grave's disease [11,38], sarcoidosis [26], primary biliary cirrhosis [25], Crohn's disease [31] and choriomeningitis [41]. It is also well known that TCR V gene usage is restricted in human T cells stimulated with superantigen [8,20] as well as in TIL of melanoma and glial tumours [27,28].…”

Enterobacterial Antigens with Tropism for Joint Structures and HLA-B27=Restricted Cytotoxic T-Cells in Reactive Arthritis

“…In more detail, Yersinia-specific B27restricted CTL preferentially used Vp13.3 and 14, autoreactive B27-restricted CTL preferred V p 13.2 and 17 (21). Interestingly, Vp gene segments 13, 14 and 17 show high sequence homologies; these TCR Vp families have also been shown to be expressed in HLA-B27-alloreactive CTL (22).…”