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Biophysics of Proteins at Surfaces: Assembly, Activation, Signaling
Poster Abstracts
14-POS
Board 14
Apotope Recognition by Anti-TRIM21 Autoantibodies in Systemic Lupus Erythematosus
N.M. Nascimento
1
, I.S. Monzó
1
, M.A. Gonzalez-Martínez
1
, S. Morais
1
, R. Puchades
1
, A.
Maquieira
1
,
David Gimenez-Romero
2
.
1
Department of Chemistry, Universitat Politècnica de València, Camino de Vera, Valencia
46022, Spain,
2
Department of Physical Chemistry, Universitat de València, Avda. Dr. Moliner
50, 46100 Burjassot, Spain.
Systemic lupus erythematosus (SLE) is related to autoimmune diseases that share several genetic
and phenotypic features. TRIM21 is a characteristic autoantigen in SLE patients, although it has
not been addressed how this protein regulates this pathology. To investigate this association, we
studied the recombinant human antigen TRIM21-IgG molecular recognition.
QCM-based studies indicated TRIM21-IgG interactions in SLE patients occurs by an antibody
bipolar bridging mechanism. These studies also confirms that the anti-TRIM21 serum only
accelerates the formation of the resulting complex, remaining unchanged the TRIM21 biological
function in SLE patients and control subjects. The peptide array-based epitope mapping indicates
that the major linear human epitope of anti-TRIM21 serum spans the amino acid sequence
LRRKQELAE. This epitope has been confirmed by computational prediction of major
histocompatibility complex class II binding regions in antigenic protein sequences, which
exclusively focused on solvent-accessible residues. For that, the structure homology modelling
for TRIM21 was made.
In view of that, the mechanism by which TRIM21 may link to the SLE is clarified. We
hypothesized that circulating autoantibodies interact with apotope of the TRIM21 protein when
this one translocates from the cytoplasm to cell surface. The anti-TRIM21 serum only reinforces
the “sensor” (immune signal induction) function of TRIM21 in translocated cells through the
TRIM21-anchored Ub-63Ub chains, leading to tissue inflammation and systemic autoimmunity.
According to our experimental data, we can relate the presence of anti-TRIM21 autoantibodies in
SLE patients with skin, heart and brain disorders, where this protein has been observed in plasma
membrane-localized form in many studies.
Acknowledgements
We acknowledges financial support from the Spanish Ministry of Economy and Competitiveness
and the European Regional Development Fund under award number CTQ2013-42914-R.
Furthermore, Noelle M. do Nascimento acknowledges the fellowship from the Generalitat
Valenciana (GRISOLIA/2012/024).