Functional role of human NK cell receptor 2B4 (CD244) isoforms.
2B4 (CD244), a member of the signaling lymphocyte-activation molecule (SLAM/CD150), is expressed on all NK cells, a subpopulation of T cells, monocytes and basophils. Human NK cells express two isoforms of 2B4, h2B4-A and h2B4-B that differ in a small portion of the extracellular domain. In the present investigation, we have studied the functions of h2B4-A and h2B4-B. Our study demonstrated that these two isoforms differ in their binding affinity for CD48, which results in differential cytotoxic activity as well as intracellular calcium release by NK cells upon target cell recognition. Analysis of the predicted 3-D structure of the two isoforms showed conformational differences that could account for their differences in binding affinity to CD48. h2B4-A was able to mediate natural cytotoxicity against CD48-expressing K562 target cells and induce intracellular calcium release, whereas h2B4-B showed no effects. NK-92MI, U937, THP-1, KU812, primary monocytes, basophils and NK cells showed expression of both h2B4-A and h2B4-B whereas YT and IL-2-activated NK cells did not show any h2B4-B expression. Stimulation of NK cells through 2B4 resulted in decreased mRNA levels of both h2B4-A and h2B4-B indicating that down-regulation of 2B4 isoforms may be an important factor in controlling NK cell activation during immune responses.
Mathew
Stephen O
SO
Department of Molecular Biology and Immunology and Institute for Cancer Research, University of North Texas Health Science Center, Fort Worth, TX 76107-2699, USA.
Rao
Krithi K
KK
Kim
Jong R
JR
Bambard
Nowland D
ND
Mathew
Porunelloor A
PA
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D000918:Antibody Specificity / Q000276:immunology; D015703:Antigens, CD / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D001402:B-Lymphocytes / Q000378:metabolism; D001491:Basophils / Q000378:metabolism; D000071178:CD48 Antigen; D020013:Calcium Signaling / Q000276:immunology; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic / Q000502:physiology; D015536:Down-Regulation / Q000276:immunology; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000235:genetics; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000187:drug effects / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008958:Models, Molecular; D011485:Protein Binding / Q000276:immunology; D011487:Protein Conformation; D020033:Protein Isoforms / Q000737:chemistry / Q000502:physiology; D020836:Protein Structure, Quaternary; D011971:Receptors, Immunologic / Q000737:chemistry / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D000071176:Signaling Lymphocytic Activation Molecule Family
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C084093:CD244 protein, human; D000071178:CD48 Antigen; C000604065:CD48 protein, human; D007141:Immunoglobulin Fc Fragments; D020033:Protein Isoforms; D011971:Receptors, Immunologic; D011993:Recombinant Fusion Proteins; D000071176:Signaling Lymphocytic Activation Molecule Family