* Laboratory of Experimental Immunology, Division of Basic Sciences, and
Intramural Research Support Program, SAIC Frederick, National Cancer Institute-FCRDC, Frederick, Maryland
Correspondence: Stephen K. Anderson, SAIC-Frederick, NCI-FCRDC, Bldg. 560, Rm. 31-93, Frederick, MD 21702-1201. E-mail: andersn{at}mail.ncifcrf.gov
Previous studies have indicated that NK cells from different strains of inbred mice may express distinct Ly49 repertoires. Screening of NK cells from the CBA/J mouse for inhibitory and activating Ly49s revealed a novel DAP12-associated receptor that was immunoprecipitated with the Ly49G-specific mAb 4D11. Degenerate primers were designed to amplify and clone Ly49 cDNAs from CBA/J NK cells. A novel activating Ly49 cDNA was identified, which bears strong homology to the partially sequenced Ly49l gene found in C57BL/6 mice. Transfection of Ly49l into a DAP12+ cell line and subsequent immunoprecipitation experiments showed that Ly49L is likely the activating Ly49 detected by the 4D11 antibody in CBA/J NK cells. Antibody-mediated cross-linking of Ly49L induced DAP12 phosphorylation, providing evidence that Ly49L is a functional activating receptor. Comparison of the extracellular domains of Ly49 family members indicates that all known activating members have an inhibitory counterpart with a highly related extracellular region.
Key Words: NK cells • Ly49 • cell surface receptors • signal transduction
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