Molecular cloning of murine intercellular adhesion molecule (ICAM-1).
We have previously reported a murine lymphocyte surface antigen MALA-2 of approximately 95,000 Mr which is expressed mainly on activated lymphocytes. The rat monoclonal antibody YN1/1 that detects this antigen profoundly inhibits mixed lymphocyte response. We have now purified MALA-2 and determined its partial amino acid sequence. By using non-redundant synthetic oligonucleotides as probes, based on the amino acid sequence, we have isolated two full length cDNA clones encoding MALA-2. The two clones are identical except for the 5' end sequence. Expression of MALA-2 on transfected COS cells is only achieved with one of the two cDNA clones. The nucleotide sequence as well as the deduced amino acid sequence of MALA-2 display striking homology with those of the recently reported human intercellular adhesion molecule ICAM-1. All the unique features of the human ICAM-1, including its homology with the neural adhesion molecule NCAM, its internal repeat structure and the immunoglobulin-like structure, are found in MALA-2. Furthermore, purified MALA-2 crosslinked to a solid support binds Con A blasts that express LFA-1, the putative receptor for ICAM-1, and the binding can be blocked by YN1/1 antibody or antimurine LFA-1 antibody indicating a direct interaction of these molecules in cell adhesion. Therefore, we consider MALA-2 to be the murine homolog of human ICAM-1. Since ICAM-1 is known to be of primary importance in immune responses and inflammatory reactions, having a monoclonal antibody and a mouse model will provide the opportunity to study the functional role of ICAM-1 in vivo.
Horley
K J
KJ
Department of Microbiology, University of British Columbia, Vancouver, Canada.
Carpenito
C
C
Baker
B
B
Takei
F
F
D000595:Amino Acid Sequence; D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics* / Q000378:metabolism; D000954:Antigens, Surface / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D015152:Blotting, Northern; D015139:Blotting, Southern; D015815:Cell Adhesion Molecules / Q000235:genetics*; D002460:Cell Line; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D016169:Lymphocyte Function-Associated Antigen-1; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D016028:Receptors, Leukocyte-Adhesion / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid; D014162:Transfection; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7
D000943:Antigens, Differentiation; D000954:Antigens, Surface; D015815:Cell Adhesion Molecules; D016169:Lymphocyte Function-Associated Antigen-1; D016028:Receptors, Leukocyte-Adhesion; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D018799:Intercellular Adhesion Molecule-1; D004247:DNA