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Recognition of Class I MHC by NK Receptor Ly-49C: Identification of Critical Residues
| Content Provider | Scilit |
|---|---|
| Author | Lian, Rebecca H. Li, Yan Kubota, Satoko Mager, Dixie L. Takei, Fumio |
| Copyright Year | 1999 |
| Description | The Ly-49 family of inhibitory receptors plays a major role in regulating mouse NK cell cytotoxicity. Two of its members, Ly-49C and I, are recognized by the mAb 5E6, which also defines a subset of NK cells involved in the hybrid resistance phenomenon. Previous studies have shown that Ly-49C binds to a broad spectrum of class I MHC molecules, while Ly-49I apparently does not bind to any class I MHC molecules tested. In the present investigation we have defined the amino acid residues of Ly-49C that are critical for determining its ligand specificities. First, using quantitative COS cell adhesion assays, we demonstrated that $Ly-49C^{B6}$ bound to $D^{d}$, $D^{b}$, $K^{b}$, or $K^{k}$ as well as to murine leukemic cell lines GM979 $(H-2^{s}$) and IC-21 $(H-2^{b}$). In contrast, COS cells expressing $Ly-49I^{B6}$ did not significantly bind to any of the class I MHC tested. To determine which amino acid residues of Ly-49C are critical for their specific binding to class I MHC, a series of chimeric and mutant Ly-49C and I were generated and tested. Exchanging the critical residues between Ly-49C and I significantly affected their binding specificities. Finally, we identified the epitopes on Ly-49C recognized by mAbs 5E6 and 4LO3311 that functionally inhibit Ly-49C recognition of its ligands. These results further define the class I specificities of Ly-49C and provide insight into the structural basis for how class I MHC is recognized by the Ly-49 family of NK receptors. |
| Ending Page | 7276 |
| Page Count | 6 |
| Starting Page | 7271 |
| ISSN | 00221767 |
| e-ISSN | 15506606 |
| DOI | 10.4049/jimmunol.162.12.7271 |
| Journal | The Journal of Immunology |
| Issue Number | 12 |
| Volume Number | 162 |
| Language | English |
| Publisher | The American Association of Immunologists |
| Publisher Date | 1999-06-15 |
| Access Restriction | Open |
| Subject Keyword | Ly 49c Recognized By Mabs Mab 5e6 Critical Residues |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology |
