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M9480211.TXT
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1994-08-09
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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
protected by Copyright Law (Title 17, U.S.Code).