MUC18/MCAM (CD146), an activation antigen of human T lymphocytes.
Extravasation and tissue infiltration of leukocytes and metastatic tumor cells require the regulated expression and function of adhesive and pro-proteolytic surface molecules. We demonstrate here that human T cells, upon activation, neo-express the melanoma metastasis-associated surface molecule MUC18/melanoma cell adhesion molecule (MCAM). Expression of MUC18/MCAM (CD146) on T cells could be identified with two mAbs (541-10B2 and 541-2E5) obtained after immunization with HUT102 T cells and found to react with activated T cells. The specificity of our mAbs for MUC18/MCAM (CD146) was revealed by 1) definition of the appropriate molecular mass of approximately 110 kDa unreduced and 120 kDa reduced, 2) reactivity of mAbs with MUC18/MCAM (CD146) cDNA-transfected mouse L cells, 3) conclusive crosswise immunoblotting experiments with MUC18/MCAM (CD146)-specific mAbs, and 4) N-terminal amino acid sequencing of precipitated protein. In vitro activation by PHA caused neo-expression of MUC18/MCAM (CD146) on peripheral blood T cells within 1 day of stimulation, reaching a maximum on day 3. In vivo expression of MUC18/MCAM (CD146) was confirmed on CD3+ T cells infiltrating delayed-type hypersensitivity lesions of the skin, on synovial fluid T cells of rheumatoid arthritis patients, and on distinct T leukemia cells. MUC18/MCAM (CD146) cell surface expression on activated T cells is mirrored by the presence of specific mRNA. Leukocytes of healthy donors do not show significant MUC18/MCAM (CD146) expression. The finding that MUC18/MCAM (CD146) is also expressed on activated T cells might suggest that this adhesion molecule is involved in the extravasation and/or homing of activated T cells.
Pickl
W F
WF
Institute of Immunology, University of Vienna, Austria.
Majdic
O
O
Fischer
G F
GF
Petzelbauer
P
P
Faé
I
I
Waclavicek
M
M
Stöckl
J
J
Scheinecker
C
C
Vidicki
T
T
Aschauer
H
H
Johnson
J P
JP
Knapp
W
W
D000911:Antibodies, Monoclonal / Q000737:chemistry; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis / Q000737:chemistry* / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology; D051929:CD146 Antigen; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000737:chemistry* / Q000276:immunology; D000939:Epitopes / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D007700:Kinetics; D008213:Lymphocyte Activation; D008545:Melanoma / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000737:chemistry* / Q000276:immunology; D008969:Molecular Sequence Data; D008970:Molecular Weight; D019006:Neural Cell Adhesion Molecules; D012333:RNA, Messenger / Q000096:biosynthesis; D013582:Synovial Fluid / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism; D014158:Transcription, Genetic / Q000276:immunology; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D051929:CD146 Antigen; D015815:Cell Adhesion Molecules; D000939:Epitopes; C497902:MCAM protein, human; D008562:Membrane Glycoproteins; D019006:Neural Cell Adhesion Molecules; D012333:RNA, Messenger