Expression of MHC class I receptors confers functional intraclonal heterogeneity to a reactive expansion of gammadelta T cells.
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.
Lafarge
Xavier
X
CNRS-UMR 5164, CIRID, IFR66, Université Bordeaux 2, Bordeaux, France.
Pitard
Vincent
V
Ravet
Sophie
S
Roumanes
David
D
Halary
Franck
F
Dromer
Claire
C
Vivier
Eric
E
Paul
Pascale
P
Moreau
Jean-François
JF
Déchanet-Merville
Julie
J
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*
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