Recognition of class I major histocompatibility complex molecules by Ly-49: specificities and domain interactions.
Ly-49 is a family type II transmembrane proteins encoded by a gene cluster on murine chromosome 6. One member of this family, Ly-49A, is expressed by a natural killer (NK) cell subset, binds to class I major histocompatibility complex (MHC) molecules, and blocks the killing of target cells bearing the appropriate H-2 antigens. Here we show that another member of this family which is expressed by an NK cell subset, Ly-49C, recognizes H-2b and H-2d structures which are distinct from and overlapping with those recognized by Ly-49A. Interactions between Ly-49A and C and their class I ligands are entirely blocked by the antibodies 5E6, YE1/48, YE1/32, and A1, all of which were found to recognize epitopes contained within the carbohydrate recognition domain (CRD). However, cell-cell binding assays revealed that class I binding specificity is conferred by a combination of sequences within both the CRD and a 19-amino acid adjacent region. We also investigated the question of whether Ly-49A and C form dimers on cells which express both receptors. When coexpressed on COS cells, sequential immunoprecipitation demonstrated that these receptors pair exclusively as homodimers, with no evidence for heterodimeric structures. These observations provide insight into both the biochemical nature of the Ly-49 family as well as the receptor functions of Ly-49C on NK cells.
Brennan
J
J
Terry Fox Laboratory, British Columbia Agency, Vancouver, Canada.
Mahon
G
G
Mager
D L
DL
Jefferies
W A
WA
Takei
F
F
D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity; D000950:Antigens, Ly / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002448:Cell Adhesion; D003429:Cross Reactions; D006183:H-2 Antigens / Q000378:metabolism*; D037181:Lectins, C-Type; D008024:Ligands; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D055650:NK Cell Lectin-Like Receptor Subfamily A; D011487:Protein Conformation; D055630:Receptors, NK Cell Lectin-Like; D011993:Recombinant Fusion Proteins / Q000378:metabolism
D000950:Antigens, Ly; D002352:Carrier Proteins; D006183:H-2 Antigens; C527088:Klra1 protein, mouse; D037181:Lectins, C-Type; D008024:Ligands; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D055650:NK Cell Lectin-Like Receptor Subfamily A; D055630:Receptors, NK Cell Lectin-Like; D011993:Recombinant Fusion Proteins