Specific binding of HLAs and antigenic peptides associated with behcet's disease and systemic sclerosis

Abstract

Human leukocyte antigen (HLA) molecules are essential components for immune functions. There play a major role to present antigenic-peptide for T-cell receptor (TCR) recognition and immune activation. Association between HLA genes and infectious as well as autoimmune diseases are identified genetic risk factors. For instance, Behçet’s disease (BD) and systemic sclerosis (SSc) are autoimmunity result in chronic of multisystemic inflammation and visceral fibrosis, respectively. To investigate the link of HLAs correlated with self-peptides for BD and SSc, molecular dynamics (MD) simulations were applied on the HLAp complexes. For BD, a self-peptide named MICA-TM was modeled for two BD-association such as HLA-A*26:01 and HLA-B*51:01 in comparisons to non-association with BD. SSc simulation were studied on the complexes of topoisomerase 1 (Top1) peptide with various HLA-DR subtypes divided into association (HLA-DRB1*08:02, HLA-DRB1*11:01 and HLA-DRB1*11:04), suspect (HLA-DRB5*01:02) and non-association (HLA-DRB1*01:01) with SSc. The unique interaction for each system was compared to the others in terms of dynamical behaviors and binding free energies. Our results showed that HLAp of diseased suspect and association exhibited high protein stability and increased binding efficiency, in contrast to non-association. Moreover, T-cell receptor bound HLA with self-peptide by minimal criteria of TCR engagement as well as infectious cases. This finding might support mechanism of BD, SSc and autoimmunity TCR-recognition leading to a more understanding and guideline on the treatment for autoimmune diseases.