Abstract:
We have studied the binding of the T-cell surface protein CD2 by anti-CD2 antibodies and by a physiologic ligand, LFA-3, using a mutational approach. Similarly, the binding of HIV to CD4, another T-cell surface protein, was studied by first examining the interaction between CD4 and anti-CD4 monoclonal antibodies. CD2 is expressed by all mature T cells. Binding of a widely distributed cell surface glycoprotein, LFA-3, by CD2 aids in the adhesion of T cells to target or antigen presenting cells. Monoclonal antibodies which recognize CD2 can block the interaction between CD2 and LFA-3 and inhibit ability of T cells to recognize antigen. In certain pairwise combinations, anti-CD2 antibodies can induce the expression of both IL-2 and IL-2 receptor in resting T cells. The latter phenomenon suggests that CD2 may play a relatively direct role in T-cell activation. Because CD2-directed activation requires the binding of monoclonal antibodies, the physiological implications of the phenomenon are somewhat obscure. In order to investigate the phenomena of CD2-directed activation, we have mapped the binding sites of a number of anti-CD2 monoclonal antibodies. Antibody binding sites were analyzed by isolating CD2 variants which no longer bind a given anti-CD2 monoclonal. This analysis revealed three antigenic regions of CD2. The CD2 binding site for LFA-3 was also examined by the mutational approach using a recombinant, soluble, form of LFA-3. Two of the antigenic regions were shown to be involved in the binding of LFA-3 by CD2. A very good correlation between the binding site of LFA-3 and the binding sites for some anti-CD2 antibodies which can cause T-cell activation was noted. CD4 is expressed by cells which recognize antigen in the context of class II MHC antigens. Interaction between CD4 and class II MHC antigens facilitates T-cell recognition of antigen by a mechanism which is not understood. CD4 also serves as a receptor for HIV. We analyzed the binding sites for a number of anti-CD4 monoclonal antibodies using the same approach used for the analysis of CD2. This analysis allowed the identification of sites of interaction between CD4 and anti-CD4 antibodies and also resulted in the identification of a region of CD4 which interacts with HIV. (Full text available from University Microfilms International, Ann Arbor, MI, as Order No. AAD89-09003)
Keywords: Antigens, CD4/*GENETICS Antigens, Differentiation, T-Lymphocyte/*GENETICS *Gene Expression Regulation, Viral Histocompatibility Antigens Class II/GENETICS Human HIV/*GENETICS Lymphocyte Transformation Receptors, Immunologic/*GENETICS T-Lymphocytes/IMMUNOLOGY THESIS 900228
M9020577
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