Identification and Molecular Cloning of p75/AIRM1, A Novel Member of the Sialoadhesin Family That Functions as an Inhibitory Receptor in Human Natural Killer Cells

doi:10.1084/jem.190.6.793

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© The Rockefeller University Press, 0022-1007/1999/9/793/ $5.00
The Journal of Experimental Medicine, Volume 190, Number 6, September 20, 1999 793-802

Identification and Molecular Cloning of p75/AIRM1, A Novel Member of the Sialoadhesin Family That Functions as an Inhibitory Receptor in Human Natural Killer Cells

Michela Falco^a,b, Roberto Biassoni^a, Cristina Bottino^a, Massimo Vitale^a, Simona Sivori^b, Raffaella Augugliaro^b, Lorenzo Moretta^a,b, and Alessandro Moretta^b
^a Istituto Nazionale per la Ricerca sul Cancro, 16132 Genova, Italy
^b Dipartimento di Medicina Sperimentale, Università degli Studi di Genova, 16132 Genova, Italy

In this study, by the generation of a specific monoclonal antibody,we identified p75/AIRM1 (for adhesion inhibitory receptor molecule1), a novel inhibitory receptor that is mostly confined to humannatural killer cells. p75/AIRM1 is a 75-kD glycoprotein that,upon sodium pervanadate treatment, becomes tyrosine phosphorylatedand associates to src homology 2 domain–bearing proteintyrosine phosphatase (SHP)-1. The p75/AIRM1 gene is locatedon human chromosome 19 and encodes a novel member of the sialoadhesinfamily characterized by three immunoglobulin-like extracellulardomains (one NH₂-terminal V-type and two C2-type) and a classicalimmunoreceptor tyrosine–based inhibitory motif (ITIM)in the cytoplasmic portion. The highest amino acid sequencesimilarity has been found with the myeloid-specific CD33 moleculeand the placental CD33L1 protein. Similar to other sialoadhesinmolecules, p75/AIRM1 appears to mediate sialic acid–dependentligand recognition.

Key Words: molecular cloning, natural killer cells, sialoadhesin, inhibitoryreceptor, immunoglobulin superfamily

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