Expansion of circulating Vγ9 / Vδ1 T cells in a patient with a syndrome of recurrent fever: evidence for an unusual antigen-driven process leading to selection of recurrent motifs within TCR junctional loops of diverse lengths

Abstract

Polyclonal expansions of human Vδ1 T cells have been described in diverse physiopathological situations without strong TCR structural data for an antigen‐driven selection. Here, we have analyzed the phenotype and TCR repertoire of γ δ T cells obtained from the peripheral blood of a 19‐year‐old patient with a syndrome of recurrent fever, which accounted for up to 40 % of CD3+ T cells and expressed predominantly Vγ9 and Vδ1 TCR regions and a memory phenotype. Sequence analysis of Vδ1‐Jδ1 transcripts derived from peripheral blood lymphocytes (PBL) indicated that, while Vδ1‐Jδ1 junctional sequences were diverse in length, all but one contained several recurrent motifs at conserved positions from both the 5′‐ and 3′‐ends of the complementarity‐determining region (CDR)3 loop. Analysis of γ δ T cell clones derived from patient PBL demonstrated that Vγ9+ but not Vγ9– T cell clones frequently expressed Vδ1 chains with these characteristics and unveiled a hierarchy between the constraints imposed on the 5′‐ vs. the 3′ motifs of the Vδ1 CDR3 loops. These results constitute the first strong evidence for a nominal antigen‐driven selection of Vδ1 T cells in vivo and also suggest that the hierarchy of the constraints imposed by antigens respectively on the length and amino acid composition of TCR CDR3 loops differs between α β and γ δ T cells.

Polyclonal, newly derived T cells with low expression of inhibitory molecule PD-1 in tonsils define the phenotype of lymphocytes in children with Periodic Fever, Aphtous Stomatitis, Pharyngitis and Adenitis (PFAPA) syndrome

“…Interestingly, the clone CALWEVYYKKL, which was highly represented in PFAPA patient no. 3, has been previously detected in the peripheral blood of a patient with periodic fever syndrome (Jouen-Beades et al, 1999). Nevertheless, the highly sensitive NGS method detected the same clone (weakly represented, 0.001%-0.1%) in all of the PFAPA and control tonsils.…”

“…However, the compartment of CD3 high DN cells does not contain solely gamma delta T cells. A T cell receptor gamma with a CALWEVYYKKL CDR3 amino acid sequence was previously described in a patient with recurrent fever and was abundant in tonsil of one PFAPA patient (Jouen-Beades et al, 1999), but it was also present in all remaining PFAPA and control tonsils. Additionally, the spectrum of other TCRG rearrangements overlapped among the PFAPA and controls.…”

The role of Vδ2-negative γδ T cells during cytomegalovirus reactivation in recipients of allogeneic stem cell transplantation

“…Dramatic expansion of V␦1 ␥␦ T cells in CMV Ϫ patient with a syndrome of recurrent fever and infection of unknown etiology has been reported. 48 A recent report by Vermijlen et al described an expansion of V␥8V␦1 cells in CMV-infected newborns. 33 We have analyzed a cohort of 35 healthy adults and found no significant difference between CMV ϩ and CMV Ϫ donors.…”

γδ+ T Cells Involvement in Viral Immune Control of Chronic Human Herpesvirus 8 Infection

“…Our observations support the model that the peripheral V␦1 T cell repertoire is shaped by positive selection in response to an antigenic stimulation (47,48).…”