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

EMBO J. 1993 Dec 15;12(13):5105-12.

Abstract

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)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antigens, Viral / chemistry*
  • Antigens, Viral / immunology
  • B-Lymphocytes / immunology*
  • Calcium / metabolism
  • Cytoplasm / ultrastructure
  • Herpesvirus 4, Human / chemistry*
  • Herpesvirus 4, Human / immunology
  • Human T-lymphotropic virus 1 / immunology
  • Interleukin-2 / biosynthesis
  • Leukemia Virus, Bovine / chemistry*
  • Leukemia Virus, Bovine / immunology
  • Lymphocyte Activation*
  • Mason-Pfizer monkey virus / immunology
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Receptor Aggregation
  • Receptors, Antigen, B-Cell / physiology
  • Signal Transduction
  • Structure-Activity Relationship
  • T-Lymphocytes / immunology*
  • Viral Envelope Proteins / chemistry*
  • Viral Envelope Proteins / immunology
  • Viral Matrix Proteins / chemistry*
  • Viral Matrix Proteins / immunology

Substances

  • Antigens, Viral
  • EBV-associated membrane antigen, Epstein-Barr virus
  • Interleukin-2
  • Receptors, Antigen, B-Cell
  • Viral Envelope Proteins
  • Viral Matrix Proteins
  • Calcium