CD94/NKG2A is a kind of inhibitory receptor belonging to C-type lectin superfamily. It specifically expresses on the surface of some lymphocytes such as NK cells and T cells, and mediates inhibitory signal. In this mini-review, the structure of CD94/NKG2A molecule is described and its biological significance is discussed.
Antigens, CD ; immunology ; HLA Antigens ; immunology ; Histocompatibility Antigens Class I ; immunology ; Humans ; Killer Cells, Natural ; immunology ; Lectins, C-Type ; immunology ; NK Cell Lectin-Like Receptor Subfamily C ; NK Cell Lectin-Like Receptor Subfamily D ; Receptors, Immunologic ; immunology ; Receptors, Natural Killer Cell ; T-Lymphocytes ; immunology

NK cell has antigen-non-specific receptors on its surface. Based on the molecular structure, NK cell receptors can be divided into two types, including Ig superfamily and C-type lectin superfamily. Based on function, NK cell receptors can be divided into activation receptors (NKAR) and inhibition receptors (NKIR). NKAR includes CD16 mediating antibody dependent cytotoxicity, NKR-P1 mediating natural cytotoxicity, KAR conjugated with DAP12 and co-stimulatory receptor. They transduce signal through the ITAM motif in their cytoplasmic region. NKIR mainly include KIR and CD94/NKG2. Their ligands are MHC-I molecules. They are closely related to the recognition of auto cells by NK cells. Inhibition of NKAR activation and cytotoxic effect of NK cells by NKIR are carried out through the ITIM motif and require co-aggregation of NKAR and NKIR.
Antigens, CD ; immunology ; Humans ; Immunity, Cellular ; Killer Cells, Natural ; immunology ; Lectins, C-Type ; immunology ; Ligands ; NK Cell Lectin-Like Receptor Subfamily C ; NK Cell Lectin-Like Receptor Subfamily D ; Receptors, IgG ; immunology ; Receptors, Immunologic ; immunology ; Receptors, KIR ; Receptors, Natural Killer Cell

Antigens, Surface ; analysis ; Antiretroviral Therapy, Highly Active ; CD28 Antigens ; analysis ; CD56 Antigen ; analysis ; HIV Infections ; drug therapy ; immunology ; Humans ; Killer Cells, Natural ; immunology ; Lectins, C-Type ; analysis ; NK Cell Lectin-Like Receptor Subfamily B ; NK Cell Lectin-Like Receptor Subfamily D ; analysis ; Receptors, Immunologic ; analysis ; Receptors, KIR

OBJECTIVETo investigate the expression and possible role of C-type lectin-like natural killer cell receptors, including CD94 and NKG2s, in extranodal NK/T-cell lymphoma, nasal type (EN-NK/T-NT).

METHODSReverse transcriptase polymerase chain reaction (RT-PCR) was used to detect the expression of CD94 and NKG2s in tissue sections of 21 cases of EN-NK/T-NT(confirmed by histology, immunohistochemistry, in-situ hybridization for Epstein-Barr virus(EBV) and PCR for T-cell receptor genes), eight midline B cell lymphomas (BCL), 10 peripheral T cell lymphoma of lymph nodes (PTCL), five spleens, five thymuses and five chronic nasopharyngitis.

RESULTSAll 21 cases of EN-NK/T-NT showed typical histological features, with expression of CD3epsilon, CD56, cytotoxic granules and positivity of EBV in 20 cases. The RT-PCR results showed a high level expression of CD94 (85.7%) and NKG2 members (95.2% totally, with NKG2A/2B in 85.7%, NKG2D in 61.9%, NKG2F in 14.3%, NKG2C/2E in 4.8%, respectively and sequentially) in EN-NK/T-NT. But in the controls, none of the receptors were detected in TCL (0%) and BCL (0%), while only a few cases of lymphoid tissues expressed one or two of these receptors (two spleens and two chronic nasopharyngitis mucosa for CD94, one spleen for NKG2A/2B and one thymus for NKG2D). The differences of CD94 and NKG2 expression between EN-NK/T-NT and BCL or TCL were statistically significant (P<0.01). Co-expression of CD94 and NKG2 was found in 17 out of 21 EN-NK/T-NT cases (81.0%).

CONCLUSIONSThe specific and sequential expression nature of CD94 and NKG2 in EN-NK/T-NT, mimics the developmental expression model in their normal counterparts, and suggests that the tumor cells of most cases are being activated and keeping in a stage as the functional NK cells. Detection of these molecules may provide a useful tool to confirm the diagnosis of NK cell lymphoma.

Adolescent ; Adult ; Aged ; Diagnosis, Differential ; Epstein-Barr Virus Infections ; virology ; Female ; Follow-Up Studies ; Herpesvirus 4, Human ; isolation & purification ; Humans ; Lymphoma, B-Cell ; metabolism ; pathology ; Lymphoma, Extranodal NK-T-Cell ; diagnosis ; metabolism ; pathology ; virology ; Lymphoma, T-Cell, Peripheral ; metabolism ; pathology ; Male ; Middle Aged ; NK Cell Lectin-Like Receptor Subfamily C ; metabolism ; NK Cell Lectin-Like Receptor Subfamily D ; metabolism ; Nose Neoplasms ; diagnosis ; metabolism ; pathology ; virology ; Survival Rate ; Young Adult

OBJECTIVETo analyze the clinicopathologic features of extranodal NK/T cell lymphoma, nasal type (ENKTCL-N), to explore the expression of NK cell-associated receptors in ENKTCL-N and the relationship with prognosis, and to establish a prognostic model.

METHODSOne hundred and twenty-six cases of ENKTCL-N were selected from the files of the Department of Pathology, West China Hospital of Sichuan University. The relevant clinical and follow-up data were collected, and the histopathology was reviewed. All specimens were stained immunohistochemically for CD16, ICAM-1 and LFA-1. RT-PCR was used to detect the expression of CD94, NKG2 and KIR. The relationship between the prognosis of ENKTCL-N, clinical features, histopathological characteristics and expression of these markers were also analyzed.

RESULTSENKTCL-N mainly occurred in middle-age and young patients (median age, 41 years). The male to female ratio was 3.2:1. Sites more commonly involved were the nose and upper aerodigestive tract whereas those for the non-nasal type were the skin and gut. Only six cases involved two or more extranodal sites. Most (86.5%, 109/126) of the patients were in clinical stages I/II. The tumors showed predominately medium-sized tumor cells and large-sized tumor cells accounted for only 9.5% (12/126). Coagulative necrosis was present in all cases. The expression rates of CD56, CD16, CD94, LFA-1 and ICAM-1 were 82.6% (95/115), 15.1% (19/126), 55.4% (41/74), 40.5% (51/126) and 0, respectively. The expression rate of NKG2 receptor was 90.5% (67/74) overall. NKG2 receptor expression was independent of CD94. The overall expression rate of KIR receptor was 33.8% (25/74) and KIR receptor restriction was not detected in 20.8% (5/24) of the cases. Follow-up data was available in all patients, with median and average survival time being 15 months and 20.2 months, respectively. Survival analysis showed that prognostic factors included the gender, age, disease type, extranodal involvement, stage, the expression of CD16, LFA-1 and CD94. Cox's proportional hazard regression analysis revealed four factors, age, involved site, stage and CD16 expression, were independent prognostic factors.

CONCLUSIONSThe age, disease type, stage and CD16 expression are independent prognostic factors. Establishment of a prognostic model based on the above four factors can be more accurate in the prognostication of ENKTCL-N. The differences in the clinical features, prognosis, and expression of NK cell-associated receptors are obvious between nasal NK-cell lymphoma and non-nasal NK-cell lymphoma.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; CD56 Antigen ; metabolism ; Child ; Female ; Follow-Up Studies ; Humans ; Intercellular Adhesion Molecule-1 ; metabolism ; Lymphocyte Function-Associated Antigen-1 ; metabolism ; Lymphoma, Extranodal NK-T-Cell ; metabolism ; pathology ; Male ; Middle Aged ; NK Cell Lectin-Like Receptor Subfamily D ; metabolism ; Neoplasm Staging ; Nose Neoplasms ; metabolism ; pathology ; Prognosis ; Proportional Hazards Models ; Receptors, IgG ; metabolism ; Receptors, KIR ; metabolism ; Receptors, NK Cell Lectin-Like ; metabolism ; Survival Rate ; Young Adult