Potential T cell epitopes of Mycobacterium tuberculosis that can instigate molecular mimicry against host: implications in autoimmune pathogenesis

Employing bioinformatics tools, we have identified potentially cross-reactive T cell epitopes restricted to predominant class I and II alleles of human leukocyte antigens (HLA). These are similar to peptides of mycobacterial proteins and considerable numbers of them are promiscuous. Some of the identified antigens corroborated with established autoimmune diseases linked with mycobacterial infection.The present study reveals many target proteins and their putative T cell epitopes that might have significant application in understanding the molecular basis of possible T cell autoimmune reactions during M. tuberculosis infections.Although, the immune system efficiently discriminates between self and non-self, the occurrence of autoimmune diseases is a testimony to the fact that such discrimination may be imprecise [1]. Understanding the etiology of autoimmune diseases has been a great challenge to immunologists. The existence of central tolerance mechanism ensures the clonal deletion of autoreactive T cells and B cells. Nonetheless, there are ample evidences signifying that a considerable number of such cells can escape these "failsafe" mechanisms [1,2]. Immunological insults like exposure to pathogenic bacteria, viruses, aberrant expression of self proteins and exposure to cryptic antigens, etc., have been implicated to trigger and amplify the immune reactions that culminate into autoimmune diseases [3-5]. Antigenic determinants/epitopes present in pathogens, which resemble the host proteins, can potentially be a threat in activating the cells of immune system, resulting in autoimmunity [3,4]. This resemblance is popularly termed as molecular mimicry.Many different autoimmune diseases have been hypothesized to be a result of this mistaken identity. As a result of molecular mimicry, the immune cells attack the host tissues [3,5]. The sharing of similar epitopes between the host and the pathogens may instigate autoaggression by stirring autoreactive T cells and B cells.