L3T4 and the immunoglobulin gene superfamily: new relationships between the immune system and the nervous system

Abstract

L3T4 is a mouse cell surface protein expressed on most thymocytes and on the subset of mature T cells that recognizes class II MHC molecules. Its primary function on T cells is most likely that of increasing the avidity of the interaction between T cells and antigen-presenting or target cells. It may accomplish this by binding to a nonpolymorphic region on class II MHC molecules. The cDNA and gene encoding L3T4 have been isolated and sequenced. Analysis of the amino acid sequence predicted by the nucleotide sequence indicates that L3T4 is a member of the Ig gene superfamily. It is most closely related to Ig and Tcr V regions. Although the amino-terminal domain of L3T4 is the portion of the molecule that is most similar to V-regions, L3T4 is one of the polydomain members of the Ig gene superfamily. Studies of the expression of L3T4 mRNA in various tissues led to the surprising finding that this gene is transcribed not only in T lymphoid cells, but also in brain. The predominant form of L3T4 mRNA expressed in brain is foreshortened as compared to that in T lineage cells, and it is most likely the product of a distinct transcriptional start site. If translated, the protein encoded by this brain transcript would be 217 amino acids in length and would lack the signal peptide and the amino-terminal 214 amino acids of the mature protein. It is not known whether a stable protein product is synthesized from this mRNA or what its function might be. However, these findings place L3T4 in an intriguing class of Ig gene superfamily members characterized by coexpression in the immune system and the nervous system.