Document 0211
 DOCN  M9480211
 TI    Cross-reactivity between autoimmune anti-U1 snRNP antibodies and
       neutralizing epitopes of HIV-1 gp120/41.
 DT    9410
 AU    Douvas A; Takehana Y; Department of Medicine, University of Southern
       California Health; Sciences Center, Los Angeles 90033.
 SO    AIDS Res Hum Retroviruses. 1994 Mar;10(3):253-62. Unique Identifier :
       AIDSLINE MED/94289063
 AB    We report extensive amino acid sequence homology between HIV-1 gp120/41,
       and > 33% of a U1 RNA-associated splicing protein, 70K. The latter is a
       target of autoimmune anti-RNP antibodies in mixed connective tissue
       disease (MCTD). The homologies, involving dominant epitopes of 70K and
       neutralizing epitopes of gp120/41, are the basis for mutual antibody
       cross-reactivity. A key finding is that the epitope GRAFVTIG in the V3
       loop of gp120 (strain IIIB) is homologous to the functionally essential
       U1 RNA-binding site of 70K. ELISA data reveal a mean reactivity of
       anti-RNP antibodies to V3 IIIB that is as high as that of HIV sera. V3
       MN, containing the framework sequence G-AF-T, also cross-reacts with
       anti-RNP antibodies, as do hydrophilic epitopes in gp41 homologous to
       the COOH end of 70K. Further, there is strong cross-reactivity between
       HIV sera and 70K in Western blots. In contrast, antibodies from a
       related autoimmune disorder, Sjogren's syndrome (SS), are neither V3 nor
       gp41 selective. We conclude that the substantial cross-reactivities
       reported here are due to conserved, antigenically dominant B cell
       epitopes having homologous counterparts in 70K and gp120/41. Because
       antibody production in both MCTD and HIV-1 infection is T cell
       dependent, the results imply that common T cell clones are also
       activated in these two disease paradigms. Further exploration of the
       mechanisms that activate these clones, and that control their divergent
       fates in MCTD and AIDS, may provide new insights into immune
       dysregulation in HIV infection.(ABSTRACT TRUNCATED AT 250 WORDS)
 DE    Amino Acid Sequence  Antigenic Determinants/IMMUNOLOGY
       Autoantibodies/*IMMUNOLOGY  Blotting, Western  Cross Reactions
       Enzyme-Linked Immunosorbent Assay  Human  HIV Antibodies/IMMUNOLOGY  HIV
       Envelope Protein gp120/*IMMUNOLOGY  HIV Envelope Protein
       gp41/*IMMUNOLOGY  HIV-1/*IMMUNOLOGY  Mixed Connective Tissue
       Disease/IMMUNOLOGY  Molecular Sequence Data  Neutralization Tests
       Ribonucleoproteins, Small, U1/*IMMUNOLOGY  Sequence Homology, Amino Acid
       JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
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