ICAM-2 peptides mediate lymphocyte adhesion by binding to CD11a/CD18 and CD49d/CD29 integrins.
Three fifteen-amino-acid polypeptides designated peptides 1, 2 and 3 were synthesised as likely candidates for mimicking the role of ICAM-2 as a ligand. The ability of each peptide to bind lymphoid cells was tested. Peptide 2 largely mediated cell attachment of unstimulated cells and this binding was only marginally increased by stimulating the cells with phorbol dibutyrate (P(Bu)2). Peptide 3 mediated minimal spontaneous cell attachment, but this binding was significantly enhanced following P(Bu)2 stimulation. Peptide 1 had no effect on cell attachment with or without stimulation. The cell attachment to peptide 2 was both temperature- and cation-dependent. Studies using specific monoclonal antibodies showed that with unstimulated cells, anti-VLA-4 alpha(CD49d) or beta chain (CD29) antibodies (KD4-13 and 4B4) and anti-CD18 (1B4) each partially inhibited the cell binding. Monoclonal antibodies against CD54 (ICAM-1; 84H10 or LB2), MHC class 1 (W6/32) and control mouse IgG had no effect. When anti-CD29 and anti-CD18 monoclonal antibodies were used concurrently, there was almost complete inhibition of the cell attachment. These observations indicated that cell adhesion via ICAM-2 is mediated: (i) predominantly by peptide 2 in unstimulated and P(Bu)2-stimulated cells, and also, to some extent, by peptide 3 in P(Bu)2-stimulated cells and (ii) by binding to both CD11/CD18 and CD49d/CD29 integrins.
Seth
R
R
Department of Chemical Pathology, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
Salcedo
R
R
Patarroyo
M
M
Makgoba
M W
MW
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000378:metabolism*; D000943:Antigens, Differentiation / Q000378:metabolism; D018845:CD11 Antigens; D018821:CD18 Antigens; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D000939:Epitopes; D039001:Integrin alpha Chains; D019012:Integrin beta1; D016023:Integrins / Q000378:metabolism*; D008214:Lymphocytes / Q000166:cytology* / Q000276:immunology; D008969:Molecular Sequence Data; D016028:Receptors, Leukocyte-Adhesion / Q000378:metabolism; D016029:Receptors, Very Late Antigen / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D018845:CD11 Antigens; D018821:CD18 Antigens; C063493:CDw49d; D015815:Cell Adhesion Molecules; D000939:Epitopes; C065289:ICAM2 protein, human; D039001:Integrin alpha Chains; D019012:Integrin beta1; D016023:Integrins; D016028:Receptors, Leukocyte-Adhesion; D016029:Receptors, Very Late Antigen