title: Expression of MHC class I receptors confers functional intraclonal heterogeneity to a reactive expansion of gammadelta 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 alphabeta T cell clones concluded that MHC-NKR expression was not a clonal attribute. Here, we examined a massive monoclonal expansion of a non-leukemic gammadelta 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(+) gammadelta 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 gammadelta T cell effector functions or proliferation upon pathogen challenge.
authors.affiliation: CNRS-UMR 5164, CIRID, IFR66, Université Bordeaux 2, Bordeaux, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Lafarge
authors.forename: Vincent
authors.initials: V
authors.lastname: Pitard
authors.forename: Sophie
authors.initials: S
authors.lastname: Ravet
authors.forename: David
authors.initials: D
authors.lastname: Roumanes
authors.forename: Franck
authors.initials: F
authors.lastname: Halary
authors.forename: Claire
authors.initials: C
authors.lastname: Dromer
authors.forename: Eric
authors.initials: E
authors.lastname: Vivier
authors.forename: Pascale
authors.initials: P
authors.lastname: Paul
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Moreau
authors.forename: Julie
authors.initials: J
authors.lastname: Déchanet-Merville
mesh_terms: D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000502:physiology*; D001483:Base Sequence; D003586:Cytomegalovirus Infections / Q000276:immunology; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D037181:Lectins, C-Type / Q000502:physiology*; D016040:Lung Transplantation; D008213:Lymphocyte Activation; D008875:Middle Aged; D008969:Molecular Sequence Data; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis / Q000502:physiology*; D011971:Receptors, Immunologic / Q000502:physiology*; D054340:Receptors, KIR; D054343:Receptors, KIR2DL2; D054344:Receptors, KIR2DL3; D055607:Receptors, Natural Killer Cell; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D015395:Histocompatibility Antigens Class I; C515077:KIR2DL2 protein, human; C527054:KLRC1 protein, human; C497869:KLRD1 protein, human; D037181:Lectins, C-Type; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D054343:Receptors, KIR2DL2; D054344:Receptors, KIR2DL3; D055607:Receptors, Natural Killer Cell