Expression of MHC class I receptors confers functional intraclonal heterogeneity to a reactive expansion of γδ T cells

Abstract

NK cell receptors for MHC class I molecules (MHC-NKR) can be expressed by T cell subsets. The restricted repertoire and phenotypic characteristics of MHC-NKR + T cells indicate that expression of MHC-NKR is acquired upon antigenic challenge and might promote expansion of T cells. Previous studies performed on in vitro generated ab T cell clones concluded that MHC-NKR expression was not a clonal attribute. Here, we examined a massive monoclonal expansion of a non-leukemic cd T cell population found in the peripheral blood of a lung-transplanted patient who suffered from a cytomegalovirus infection. Despite their monoclonality, these T cells displayed a heterogeneous and stable in vivo Ig-and lectin-like MHC-NKR phenotype. Twenty percent of the cells displayed a CD94 + NKG2A + phenotype, and 10% were labeled with an anti-CD158b1/b2/j monoclonal antibody. A CD158b/j + cd T cell clone derived in vitro from patient's peripheral blood lymphocytes was shown to express the activating form CD158j (KIR2DS2), which once cross-linked stimulated the clone cytolytic function and costimulated the TCR-induced production of cytokines, independently of the killer-activating receptor-associated protein (KARAP). In conclusion, heterogeneity of MHC-NKR expression confers a functional intraclonal diversity that may participate to induction of specific cd T cell effector functions or proliferation upon pathogen challenge.

Clonal selection in the human Vδ1 T cell repertoire indicates γδ TCR-dependent adaptive immune surveillance

“…The LES TCR, which directly binds Endothelial Protein C Receptor36, conceivably represents a molecular exemplar of Vδ2 neg adaptive immune surveillance. Naturally expanded during acute CMV infection to∼20% of total T cells, the LES clone was CD28 neg CD45RO neg , suggestive of an effector phenotype40. Also, the LES TCR utilizes a highly complex TCRδ rearrangement (incorporating 14 N/P additions) and a simpler TCRγ chain, typical of many of the Vδ2 neg dominant clonotypes we observed in this study.…”

Common Features of γδ T Cells and CD8+αβ T Cells Responding to Human Cytomegalovirus Infection in Kidney Transplant Recipients

“…Because the quality of the signal delivered by CD158 molecules depends on the composition of the intracellular part of the individual receptor or associated molecules, it is difficult to speculate on their precise action; however, these NK receptors may play an important role in the control of T cell activation when the virus persists and coexists with its host for many years [21]. Previously, we showed that CD158j expression confers an enhanced T cell receptor-induced cytotoxic activity to Vd2 neg gd T cells isolated from a CMV-infected kidney transplant recipients, compared with their CD158-negative counterparts [30].…”

Repertoire Development and the Control of Cytotoxic/Effector Function in Human γδ T Cells

“…In addition to the characteristic TCR, γ δ T cells also possess a variety of NK cell receptors including the activating receptor NKG2D [110], the inhibitory NKG2A, and killer immunoglobulin-like receptors (KIR) [111, 112]; the KIR family of receptors can be activating or inhibitory [113]. NKG2D recognizes the MHC-class I-related molecules MICA and MICB, as well as the UL-16 binding proteins (ULBP), all of which are expressed frequently on transformed cells and deliver activating signals [55, 114].…”