Differential role of distinct determinants of intercellular adhesion molecule-1 in immunologic phenomena.
This study analyzed 1) the relationship between the molecules recognized by anti-intercellular adhesion molecule-1 (ICAM-1) mAb RR 1/1 and by anti-96K melanoma-associated Ag mAb CL203.4 in lymphoid cells, 2) the induction of ICAM-1 on activated PBMC, and 3) the functional activity of distinct and spatially distant determinants recognized by mAb CL203.4 and RR1/1. Sequential immunoprecipitation experiments showed that the determinant recognized by mAb CL203.4 is expressed on a slightly broader population of ICAM-1 molecules than that defined by mAb RR1/1. Serologic and immunochemical assays have shown that ICAM-1 is induced on lymphocytes activated with Con A, PHA-M, IL-2, allogeneic HLA mismatched lymphocytes and autologous PHA-M-activated T cells. However, ICAM-1 was not detected on lymphocytes incubated with IFN-gamma. Incubation of monocytes with LPS induced ICAM-1 in the subpopulation which lacks it and increased its density on the cells which express it. Induction of ICAM-1 is an early event in the activation process and precedes the appearance of IL-2 and transferrin receptors. Comparison of the functional activity of the anti-ICAM-1 mAb CL203.4 and RR1/1 showed that both of them inhibit to a similar extent proliferation of lymphocytes stimulated with PHA-M and with allogeneic lymphocytes, but that only mAb RR1/1 inhibits PMA-induced aggregation of cultured B lymphoid cells JY, of promonocytic cells U-937 and of PHA-blasts as well as LAK cell-mediated cytotoxicity of target cells. mAb CL203.4 represents the first example of anti-ICAM-1 mAb without inhibitory effect on the aggregation of lymphoid cells. The differential functional activity of mAb CL203.4 and RR1/1 does not reflect differences in their affinity, because they display a similar affinity constant to lymphoid cells. These results suggest that distinct determinants of ICAM-1 play a different role in immunologic phenomena.
Maio
M
M
Division of Experimental Oncology 2, C.R.O., Aviano, Italy.
Tessitori
G
G
Pinto
A
A
Temponi
M
M
Colombatti
A
A
Ferrone
S
S
D000911:Antibodies, Monoclonal / Q000502:physiology; D000937:Antigen-Antibody Reactions; D000951:Antigens, Neoplasm; D000954:Antigens, Surface / Q000096:biosynthesis / Q000276:immunology*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D015815:Cell Adhesion Molecules; D002449:Cell Aggregation / Q000187:drug effects; D004306:Dose-Response Relationship, Immunologic; D000939:Epitopes / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D008262:Macrophage Activation; D058950:Melanoma-Specific Antigens; D008970:Molecular Weight; D009363:Neoplasm Proteins / Q000276:immunology; D010835:Phytohemagglutinins; D013329:Structure-Activity Relationship; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D015815:Cell Adhesion Molecules; D000939:Epitopes; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D010835:Phytohemagglutinins; D013755:Tetradecanoylphorbol Acetate