LAG-3, a novel lymphocyte activation gene closely related to CD4.
We have identified a novel human gene of the Ig superfamily, designated LAG-3. Expression of this gene is undetectable in resting PBL, while it is found (a 2-kb message) in activated T and NK cells. The LAG-3 gene includes eight exons; the corresponding cDNA encodes a 498-amino acid membrane protein with four extracellular IgSF domains. The first one belongs to the V-SET; it is particular since it includes an extra loop in the middle of the domain and an unusual intrachain disulphide bridge. The three other domains belong to the C2-SET. Strong internal homologies are found in the LAG-3 molecule between domains 1 and 3, as well as between domains 2 and 4. It is therefore likely that LAG-3 has evolved by duplication of a pre-existing gene encoding a two IgSF-domain structure. The compared analysis of LAG-3 and CD4, with respect to both their peptidic sequence as well as their exon/intron organization, indicated that the two molecules are closely related. This point is strengthened by the finding that both genes are located on the distal part of the short arm of chromosome 12.
Laboratoire d'Immunologie Cellulaire, Institut Gustave-Roussy, Villejuif, France.
F
F
Triebel
S
S
Jitsukawa
E
E
Baixeras
S
S
Roman-Roman
C
C
Genevee
E
E
Viegas-Pequignot
T
T
Hercend
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000235:genetics; D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D015152:Blotting, Northern; D015139:Blotting, Southern; D015704:CD4 Antigens / Q000235:genetics*; D002460:Cell Line; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D015723:Gene Library; D006801:Humans; D008213:Lymphocyte Activation / Q000235:genetics*; D008969:Molecular Sequence Data; D011487:Protein Conformation; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid
D015703:Antigens, CD; D015704:CD4 Antigens; D012313:RNA; D004247:DNA