MOLECULAR-CLONING, EXPRESSION, AND CHROMOSOMAL LOCALIZATION OF THE HUMAN EARLIEST LYMPHOCYTE-ACTIVATION ANTIGEN AIM CD69, A NEW MEMBER OF THE C-TYPE ANIMAL LECTIN SUPERFAMILY OF SIGNAL-TRANSMITTING RECEPTORS/

The activation of T lymphocytes, both in vivo and in vitro, induces th e expression of CD69. This molecule, which appears to be the earliest inducible cell surface glycoprotein acquired during lymphoid activatio n, is involved in lymphocyte proliferation and functions as a signal t ransmitting receptor in lymphocytes, natural killer (NK) cells, and pl atelets. To determine the structural basis for CD69 function, the cDNA coding for CD69 was isolated by a polymerase chain reaction-based str ategy using oligonucleotides deduced from peptide sequences of the pur ified protein. The isolated cDNA exhibited a single open reading frame of 597 bp coding for CD69, and predicted a 199-amino acid protein of type II membrane topology, with extracellular (COOH-terminal), transme mbrane, and intracellular domains. The CD69 clone hybridized to a 1.7- kb mRNA species, which was rapidly induced and degraded after lymphocy te stimulation, consistent with the presence of rapid degradation sign als at the 3' untranslated region. Transient expression of the polypep tide encoded by CD69 cDNA in COS-7 cells demonstrated that it presente d properties comparable to native CD69 protein. The CD69 gene was regi onally mapped to chromosome 12 p13-p12 by both somatic cell hybrid DNA analysis and fluorescence in situ hybridization coupled with GTG band ing (G bands by trypsin using Giemsa). Protein sequence homology searc h revealed that CD69 is a new member of the Ca2+-dependent (C-type) le ctin superfamily of type II transmembrane receptors, which includes th e human NKG2, the rat NKR-P1, 2nd the mouse NKR-P1 families of NK cell -specific genes. CD69 also has structural homology with other type II lectin cell surface receptors, such as the T cell antigen Ly49, the lo w avidity immunoglobulin E receptor (CD23), and the hepatic asialoglyc oprotein receptors. The CD69 protein also shares functional characteri stics with most members of this superfamily, which act as transmembran e signaling receptors in early phases of cellular activation.