title: Receptors for HLA class-I molecules in human natural killer cells.
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 class I alleles leads to NK-mediated target cell lysis. During NK cell development, the class I-specific receptors have adapted to self-class I molecules on which they recognize epitopes shared by groups of class I alleles. As such, they may fail to recognize either self-molecules that bound unusual peptides or allogeneic class I molecules unrelated to self-alleles. Different types of receptors specific for groups of HLA-C or HLA-B alleles have been identified. While in most instances, they function as inhibiting receptors, an activating form of the HLA-C-specific receptors has been identified in some donors. Molecular cloning of HLA-C- and HLA-B-specific receptors has revealed new members of the immunoglobulin superfamily with two or three Ig-like domains, respectively, in their extracellular portion. While the inhibiting form is characterized by a long cytoplasmic tail associated with a nonpolar transmembrane portion, the activating 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 cytolytic T lymphocytes expresses NK-type class I-specific receptors. These receptors exert an inhibiting activity on T cell receptor-mediated functions and offer a valuable model to analyze the regulatory mechanisms involved in receptor-mediated cell activation and inactivation.
authors.affiliation: Dipartimento di Scienze Biomediche e Biotecnologie, Universita di Brescia, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Moretta
authors.forename: C
authors.initials: C
authors.lastname: Bottino
authors.forename: M
authors.initials: M
authors.lastname: Vitale
authors.forename: D
authors.initials: D
authors.lastname: Pende
authors.forename: R
authors.initials: R
authors.lastname: Biassoni
authors.forename: M C
authors.initials: MC
authors.lastname: Mingari
authors.forename: L
authors.initials: L
authors.lastname: Moretta
mesh_terms: D000818:Animals; D006680:HLA Antigens / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D007694:Killer Cells, Natural / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000502:physiology*
chemical_list: D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D011971:Receptors, Immunologic