The (YXXL/I)2 signalling motif found in the cytoplasmic segments of the bovine leukaemia virus envelope protein and Epstein-Barr virus latent membrane protein 2A can elicit early and late lymphocyte activation events.
The cytoplasmic domains of the transducing subunits associated with B and T cell antigen receptors contain a common amino acid motif consisting of two precisely spaced Tyr-X-X-Leu/Ile sequences (where X corresponds to a variable residue). Expression of a single copy of this motif suffices to initiate B or T cell activation. The bovine leukaemia virus (BLV) is a B cell lymphotropic retrovirus which causes a non-neoplasic proliferation of B cells. The cytoplasmic domain of the BLV transmembrane envelope glycoprotein, gp30, possesses two overlapping copies of the Tyr-X-X-Leu/Ile-containing motif which could participate in the induction of B cell activation. Similarly, the N-terminal cytoplasmic domain of the latent membrane protein 2A (LMP2A) of the Epstein-Barr virus (EBV) contains a single copy of the Tyr-X-X-Leu/Ile-containing motif which could play a critical role in B cell transformation. To determine whether these two virus-encoded cytoplasmic domains are endowed with signalling functions, we constructed chimeric proteins by replacing the cytoplasmic tail of CD8-alpha with that of either BLV gp30 or EBV LMP2A. We show here that, once separately expressed in B or T cell lines, these chimeras are capable of triggering both calcium responses and cytokine production when cross-linked with an antibody to CD8-alpha. Furthermore, using site-directed mutagenesis, we demonstrated unequivocally that this signalling function may be accounted for by the Tyr-X-X-Leu/Ile motifs they contain.(ABSTRACT TRUNCATED AT 250 WORDS)
Beaufils
P
P
Centre d'Immunologie INSERM-CNRS de Marseille-Luminy, France.
Choquet
D
D
Mamoun
R Z
RZ
Malissen
B
B
D000595:Amino Acid Sequence; D000956:Antigens, Viral / Q000737:chemistry* / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D002118:Calcium / Q000378:metabolism; D003593:Cytoplasm / Q000648:ultrastructure; D004854:Herpesvirus 4, Human / Q000737:chemistry* / Q000276:immunology; D015368:Human T-lymphotropic virus 1 / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis; D001909:Leukemia Virus, Bovine / Q000737:chemistry* / Q000276:immunology; D008213:Lymphocyte Activation; D016093:Mason-Pfizer monkey virus / Q000276:immunology; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011940:Receptor Aggregation; D011947:Receptors, Antigen, B-Cell / Q000502:physiology; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000276:immunology; D014763:Viral Matrix Proteins / Q000737:chemistry* / Q000276:immunology
D000956:Antigens, Viral; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D007376:Interleukin-2; D011947:Receptors, Antigen, B-Cell; D014759:Viral Envelope Proteins; D014763:Viral Matrix Proteins; D002118:Calcium