DEFINITION OF A DISCONTINUOUS IMMUNODOMINANT EPITOPE AT THE NH2 TERMINUS OF THE LA SS-B RIBONUCLEOPROTEIN AUTOANTIGEN

MCNEILAGE, LJ; UMAPATHYSIVAM, K; MACMILLAN, E; GUIDOLIN, A; Whittingham, S; GORDON, T

Author(s): MCNEILAGE, LJ; UMAPATHYSIVAM, K; MACMILLAN, E; GUIDOLIN, A; Whittingham, S; GORDON, T;
Details: Publication Year 1992-05,Volume 89,Issue #5,Page 1652-1656
Journal Title: JOURNAL OF CLINICAL INVESTIGATION
Publication Type: Journal Article
Abstract: High-titer IgG autoantibodies to the La/SS-B ribonucleoprotein (RNP) are a hallmark of patients with primary Sjogren's syndrome. Anti-La/SS-B-positive human sera bind to multiple epitopes on recombinant La/SS-B, although the initial response is against an immunodominant epitope within the first 107 NH2-terminal amino acids (aa). Sequence analysis has identified a striking homology between aa 88-101 in this NH2-terminal region of La/SS-B and a feline retroviral gag polypeptide suggesting the anti-La/SS-B response may be initiated by cross-reactivity with an exogenous agent. In the present study, detailed mapping of this NH2-terminal epitope, using recombinant La/SS-B purified from the expression of overlapping DNA fragments spanning aa 1-107, has shown that this immunodominant epitope is a complex conformational or discontinuous epitope dependent upon both aa 12-28 and 82-99 for expression, even though these regions share no homology with each other. This requirement questions the significance of the homology between La/SS-B and a retroviral gag polypeptide in the generation of the B cell response to La/SS-B and is in accord with the general concept that B cells recognize conformational epitopes on antigens rather than small linear peptide sequences. The finding also reinforces the notion that native autoantigen could be the initiator of the autoimmune response.
Publisher: ROCKEFELLER UNIV PRESS
Keywords: SYSTEMIC LUPUS-ERYTHEMATOSUS; PRIMARY SJOGRENS-SYNDROME; HUMAN AUTO-ANTIGEN; AUTOIMMUNE-RESPONSE; MOLECULAR MIMICRY; PROTEIN; DNA; AUTOANTIBODIES; IDENTIFICATION; ANTIBODIES
Publisher's Version: https://doi.org/10.1172/JCI115762
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 1992-05-01 12:00:00