T-cell epitopes are important components of the inappropriate response of the immune system to self-
proteins in
autoimmune diseases. In this study, the candidate
T-cell epitopes of the La/SSB
autoantigen, the main target of the autoimmune response in patients with
Sjogren's Syndrome (SS), and
Systemic Lupus Erythematosus (SLE) were predicted using as a template the HLA-DQ2 and DQ7 molecules, which are genetically linked to patients with SS and SLE. Modeling of DQ2 and DQ7 was based on the crystal structure of
HLA-DQ8, an HLA molecule of high risk factor of type I diabetes, which is also an
autoimmune disease. The quality and reliability of the modeled DQ2 and DQ7 was confirmed by the Ramachandran plot and the TINKER molecular modeling software. Common and/or similar candidate
T-cell epitopes, obtained by comparing three different approaches the Taylor's sequence pattern, the TEPITOPE quantitative matrices, and the MULTIPRED artificial neural network, were subjected to homology modeling with the crystal structure of the
insulin-B
peptide complexed with
HLA-DQ8, and the best superposed candidate
epitopes were placed into the modeled HLA-DQ2 and DQ7 binding grooves to perform energy minimization calculations. Six
T-cell epitopes were predicted for
HLA-DQ7 and nine for HLA-DQ2 covering parts of the amino-terminal and the central regions of the La/SSB
autoantigen. Residues corresponding to the P1, P4, and P9 pockets of the HLA-DQ2 and DQ7 binding grooves experience very low SASA because they are less exposed to the microenvironment of the groove. The proposed
T-cell epitopes complexed with HLA-DQ2/DQ7 were further evaluated for their binding efficiency according to their potential interaction energy, binding affinity, and IC50 values. Our approach constitutes the ground work for a rapid and reliable experimentation concerning the
T-cell epitope mapping of
autoantigens, and could lead to the development of T-cell inhibitors as immunotherapeutics in
autoimmune diseases.