Molecular mimicry and the role of B lymphocytes in the processing of autoantigens

Abstract

The immune system has evolved several mechanisms that provide lymphocytes with the intelligence to ignore self proteins while attacking foreign pathogenic agents. Notably, B and T lymphocytes that encounter self antigen at either the inappropriate levels or affinity are usually instructed to perish or become anergized. However, the presence of autoimmune disease suggests that the induction of self tolerance is not foolproof. In fact, autoreactive cells are now found to be normal inhabitants of the B and T lymphocyte repertoire. This review examines how foreign peptides which resemble self proteins can elicit autoimmunity that is amplified to many sites on a target autoantigen. In particular, B lymphocytes initiated by foreign molecular mimics can process and present self peptides in the shaping of autoimmune T cell responses.

Key Sequences Involved in the Spreading of the Systemic Autoimmune Response to Spliceosomal Proteins

“…These findings combined with those obtained in the case of chromatin, suggest that the target of autoantibodies is most probably the intact particle rather than its individual constituents, and highlight the importance of its structural integrity for epitope spreading [20±23]. A model involving B-and T-cell participation in the context of epitope spreading was proposed by Mamula et al [6,8,24]. In this model, professional antigen-presenting cells (APCs) present either foreign cross-reactive antigens or cryptic self determinants in an initial priming of T cells, which in turn, provide help to autoreactive B cells (Fig.…”

“…Based on the observation that in autoimmune individuals the response is never generalized but is specifically oriented, it has been proposed that molecular mimicry of viral or bacterial antigens with self determinants q 2001 Blackwell Science Ltd might be one of the pathogenic mechanisms in the autoimmune disease [4,5]. Several examples of molecular mimicry have been reported including epitopes from group A Streptococcus, herpes simplex virus, Epstein±Barr virus and several retroviruses [6]. The difficulty to demonstrate the direct involvement of a particular pathogen in autoimmunity arise from the fact that owing to a certain degree of plasticity' or promiscuity of the T-lymphocyte receptors, it is not necessary for the foreign antigens to share an identical sequence with self antigens in order to activate autoimmune T cells [7].…”

Infection, mimics, and autoimmune disease

“…Cross-reaction between the mammalian and trypanosomal peptides was documented for both T and B cells. The finding that this peptide bears both B-and T-cell epitopes makes it a leading candidate for the induction of the cardiomegaly of Chagas' disease through molecular mimicry, since it would facilitate T/B-cell cooperation (8).…”

Introduction: Epitope mimicry as a component cause of autoimmune disease

“…Crossreactivity at the T cell level is a most significant finding since the driving force behind the pathogenesis of autoimmune diseases is essentially the T cell response. The second important finding is the demonstration that exogenous antigen that mimics endogenous antigen can be processed and presented by B cells such that autoimmune T cells are primed against the endogenous antigen [11]. Linked with this is the demonstration of epitope spreading of immune responses to new epitopes of a target antigen (intramolecular spreading) or determinants of another antigen (intermolecular spreading) [8].…”

“…The next section focuses on the mechanisms of mimicry. Liang and Mamula [11] review the capacity of B cells primed with foreign antigen to activate autoreactive T cells to respond to similar endogenous antigen. Farris and colleagues [12] review the role of determinant spreading in the progression to autoimmune disease and provide a description of the pathways to autoimmunity, for which mimicry may well be a component.…”