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Updated: May 6, 2026
A High Throughput MHC II Binding Assay for Quantitative Analysis of Peptide Epitopes
Published on: March 25, 2014
HLA variation analysis and autoantigen epitope prediction in idiopathic inflammatory myopathies
Bandana Jassal1, Gouri Chopra1, Aishwarya Dhall1
1Neuropathology Laboratory, Neurosciences Centre, All India Institute of Medical Sciences, New Delhi, India.
Objective:
To identify HLA associations with clinical and autoantibody-defined subgroups of idiopathic inflammatory myopathy (IIM) and predict potential immunogenic epitopes presented by subgroup-specific HLA alleles.
Methods:
An observational case-control study was conducted including 147 biopsy-confirmed IIM patients and 114 ethnically matched healthy controls. Patients were classified into clinical and autoantibody-defined subgroups. High-resolution HLA genotyping was performed, and allele/amino acid frequencies were compared between the groups. Epitope prediction was carried out for key HLA-associated autoantibody subgroups using in silico tools assessing antigenicity, allergenicity, toxicity and molecular docking with HLA alleles.
Results:
HLA-C*07:01 was protective in IIM (Pa = 1.23 × 10-2, OR = 0.17, 95% CI 0.06-0.41). Subgroup analysis showed associations of HLA-A*33:03 with DM (Pa = 3.97 × 10-3, OR = 14.8, 95% CI 4.38-68.07) and DQB1*06:03 with PM (Pa = 2.40 × 10-2, OR = 7.24, 95% CI 2.42-22.61). The anti-Mi2 subgroup showed strong associations with A*33:03 (Pa = 2.82 × 10-3, OR = 19.73, 95% CI 5.11-98.01), DQA1*02:01 (Pa = 1.03 × 10-2, OR = 10.28, 95% CI 2.33-53.75) and DQB1*03:03 (Pa = 1.98 × 10-2, OR = 8.99, 95% CI 2.71-30.51). Anti-Ro52 was associated with B*08:01 (Pa = 2.94 × 10-3, OR = 11.67, 95% CI 3.56-39.83). Fine mapping pinpointed phenylalanine at position 25 of DQA1 to the risk allele DQA1*02:01 in anti-Mi2a/b autoantibody positive patients. From 49 predicted Mi-2 peptides, 'YYKYILTR', 'QAFSRAHR' and 'DYWEKLLR' bound stably to A*33:03 and were non-allergenic and non-toxic.
Conclusion:
In the anti-Mi2 subgroup, we identified novel HLA alleles, amino acid variants and immunogenic epitopes, supporting a role for HLA-restricted antigen presentation in disease pathogenesis and indicating candidate targets for antigen-specific immunotherapy. However, the HLA/epitope findings related to anti-Mi2 are exploratory due to limited power, and require confirmation in larger cohorts together with experimental validation.
