CATERPILLER 16.2 (CLR16.2), a Novel NBD/LRR Family Member That Negatively Regulates T Cell Function

• Published in: The Journal of biological chemistry Vol. 280; no. 18; pp. 18375 - 18385
• Main Authors: Conti, Brian J., Davis, Beckley K., Zhang, Jinghua, O'Connor, William, Williams, Kristi L., Ting, Jenny P.-Y.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 06.05.2005; American Society for Biochemistry and Molecular Biology
• Subjects: Amino Acid Sequence; Carrier Proteins - genetics; Carrier Proteins - metabolism; Carrier Proteins - physiology; Cloning, Molecular; Down-Regulation - immunology; HeLa Cells; Humans; Intercellular Signaling Peptides and Proteins - genetics; Intercellular Signaling Peptides and Proteins - isolation & purification; Intercellular Signaling Peptides and Proteins - physiology; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - metabolism; Jurkat Cells; Membrane Proteins - genetics; Membrane Proteins - metabolism; Membrane Proteins - physiology; Molecular Sequence Data; Multigene Family; Nod2 Signaling Adaptor Protein; Oligonucleotide Array Sequence Analysis; Peptide Fragments - genetics; Peptide Fragments - metabolism; Receptors, Antigen, T-Cell - genetics; Receptors, Antigen, T-Cell - physiology; T-Lymphocytes - metabolism; T-Lymphocytes - physiology
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M413169200

The newly discovered mammalian CATERPILLER (NOD, NALP, PAN) family of proteins share similarities with the NBD-LRR superfamily of plant disease resistance (R) proteins and are predicted to mediate important immune regulatory function. This report describes the first cloning and characterization of a novel CATERPILLER gene, CLR16.2 that is located on human chromosome 16. The protein encoded by this gene has a typical NBD-LRR configuration. Analysis of CLR16.2 suggests the highest expression among T lymphocytes. Cellular localization studies of CLR16.2 revealed that it is a cytoplasmic protein. Querying microarray studies in the public data base showed that CLR16.2 was significantly (>90%) down-regulated 6 h after anti-CD3 and anti-CD28 stimulation of primary T lymphocytes. Its reduction upon T cell stimulation is consistent with a potential negative regulatory role. Indeed CLR16.2 decreased NF-κB, NFAT, and AP-1 induction of reporter gene constructs in response to T cell activation by anti-CD3 and anti-CD28 antibodies or PMA and ionomycin. Following T cell stimulation, the presence of CLR16.2 reduced the levels of the endogenous transcripts for the IL-2 and CD25 proteins that are central in maintaining T cell activation and preventing T cell anergy. This reduction was accompanied by a delay of IκBα degradation. We propose that CLR16.2 serves to attenuate T cell activation via TCR and co-stimulatory molecules, and its reduction during T cell stimulation allows the ensuing cellular activation.