title: The molecular basis of natural killer (NK) cell recognition and function.
abstract: Natural Killer cells are likely to play an important role in the host defenses because they kill virally infected or tumor cells but spare normal self-cells. The molecular mechanism that explains why NK cells do not kill indiscriminately has recently been elucidated. It is due to several specialized receptors that recognize major histocompatibility complex (MHC) class I molecules expressed on normal cells. The lack of expression of one or more HLA class I alleles leads to NK-mediated target cell lysis. Different types of receptors specific for groups of HLA-C, HLA-B, and, very recently, HLA-A alleles have been identified. While in most instances, they function as inhibitory receptors, an activatory form of the HLA-C-specific receptors has been identified in some donors. Molecular cloning of HLA-C-, HLA-B- or HLA-A-specific receptors has revealed new members of the immunoglobulin superfamily with two or three Ig-like domains, respectively, in their extracellular portion. While the inhibitory form is characterized by a long cytoplasmic tail associated with a non-polar transmembrane portion, the activatory one has a short tail associated with a Lys-containing transmembrane portion. Thus, these human NK receptors are different from the murine Ly49, that is a type II transmembrane protein characterized by a C-type lectin domain. A subset of activated T lymphocytes expresses NK-type class I-specific receptors. These receptors exert an inhibiting activity on T cell receptor-mediated functions and may provide an important mechanism of downregulation of T cell responses.
authors.affiliation: Istituto Scientifico Tumori e Centro Biotecnologie Avanzate, Genova, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Moretta
authors.forename: M C
authors.initials: MC
authors.lastname: Mingari
authors.forename: D
authors.initials: D
authors.lastname: Pende
authors.forename: C
authors.initials: C
authors.lastname: Bottino
authors.forename: R
authors.initials: R
authors.lastname: Biassoni
authors.forename: A
authors.initials: A
authors.lastname: Moretta
mesh_terms: D017951:Antigen Presentation / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008967:Molecular Biology; D011946:Receptors, Antigen / Q000235:genetics / Q000276:immunology
chemical_list: D011946:Receptors, Antigen