Document 0522
 DOCN  M9590522
 TI    Modulation of CD4 lateral interaction with lymphocyte surface molecules
       induced by HIV-1 gp120.
 DT    9509
 AU    Dianzani U; Bragardo M; Buonfiglio D; Redoglia V; Funaro A; Portoles P;
       Rojo J; Malavasi F; Pileri A; Dipartimento di Scienze Mediche,
       Universita di Torino, Italy.
 SO    Eur J Immunol. 1995 May;25(5):1306-11. Unique Identifier : AIDSLINE
       MED/95293027
 AB    CD4, a lymphocyte surface glycoprotein, serves as co-receptor for
       antigen with the T cell receptor (TCR). It is also the lymphocyte
       receptor for HIV by binding the gp120 viral envelope protein.
       Interaction of gp120 with CD4 is crucial for viral infection, but is not
       sufficient to allow viral entry into cells. Recombinant gp120 alters
       CD4+ T cell responsiveness to activation stimuli. To express its
       co-receptor function fully, CD4 must be laterally associated with the
       TCR and CD45 to form multi-receptor complexes competent to transduce
       potent activation signals. Here, we examine the possibility that
       gp120/CD4 binding alters lateral associations of CD4 with other
       lymphocyte surface molecules, and that assembly of abnormal
       multi-molecular complexes is involved in the gp120-induced CD4+ T cell
       dysfunction and in viral entry. In the absence of gp120, CD4 displayed
       high association with CD3, CD5, CD45RC, CD25, CD28, CD44, and CD53; weak
       association with CD2, CD38, CD45RB, CD62L, and CD26; and no association
       with CD45RA, CD45RO, CD11b, CD11a, CD54, CD7, CD48, CD98, CD59 CD55, HLA
       class I and class II molecules. Treatment with gp120 significantly
       increased CD4 association with CD3, CD45RA, CD45RB, CD59, CD38, CD26 and
       HLA class I, and decreased that with CD45RC. Specificity of these
       results were assessed at various levels. First, gp120 did not influence
       lateral associations displayed by other molecules, such as HLA class II.
       Second, the Leu3 mAb which binds CD4 on a site overlapping the gp120
       binding site, did not elicit the same CD4 lateral associations as gp120,
       and finally, a direct gp120/CD4+ interaction was needed to induce the
       lateral associations, as shown by the observation that blocking the
       gp120/CD4 binding by the Leu3 mAb inhibited the gp120-induced
       associations. These results can be interpreted in several ways gp120/CD4
       interaction could trigger an inside-out signal responsible for the
       associations, or gp120 could induce steric modifications of CD4 that
       increase its affinity for the associating molecules. Alternatively,
       these molecules may interact directly with gp120, bridging them with
       CD4.It is also possible that th e associations may be mediated by
       additional components, interacting with both gp120 and the associating
       surface molecule. The last hypothesis is likely for CD59, whose
       gp120-induced association with CD4 required the presence of serum in the
       co-capping assay. Since both CD59 and gp120 bind complement, the
       observed association could be mediated by complement components.
 DE    Antibodies, Monoclonal/IMMUNOLOGY  Antigens, CD/IMMUNOLOGY/*METABOLISM
       Antigens, CD26/PHYSIOLOGY  Antigens, CD4/*METABOLISM  Antigens,
       CD45/IMMUNOLOGY/*METABOLISM  Antigens, Surface/*METABOLISM
       Complement/PHYSIOLOGY  Culture Media, Serum-Free  CD4-Positive
       T-Lymphocytes/*IMMUNOLOGY  Human  HIV Envelope Protein
       gp120/METABOLISM/*PHARMACOLOGY  HIV-1/*IMMUNOLOGY  HLA
       Antigens/IMMUNOLOGY  Immunologic Capping/*DRUG EFFECTS  *Lymphocyte
       Transformation  Macromolecular Systems  Membrane
       Glycoproteins/METABOLISM  Protein Binding/DRUG EFFECTS  Receptors,
       Antigen, T-Cell, alpha-beta/IMMUNOLOGY/*METABOLISM  Signal Transduction
       Support, Non-U.S. Gov't  T-Lymphocyte Subsets/*IMMUNOLOGY/METABOLISM
       JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).