Mycoplasma arthritidis-Derived Superantigen (MAM), a Unique Class of Superantigen That Bridges Innate and Adaptive Immunity

Abstract

This chapter begins with an outline of the original observations that led to the discovery of Mycoplasma arthritidis-derived superantigen (MAM) and discusses the structural basis of its interaction with class II major histocompatibility complex (MHC) molecules and T-cell receptors (TCRs). It reviews recent work on the interaction of MAM with Toll-like receptors and their importance in control of innate and adaptive immunity and in disease expression. The chapter discusses the potential role of MAM-like superantigens (SAgs) in autoimmune disease and how this might relate to recent findings on Toll-like receptor (TLR) control of adaptive immunity. Antigen-induced activation of T cells leading to cytokine production and proliferation requires signals delivered by antigen-presenting cells (APC), i.e., macrophages or dendritic cells (DCs), through costimulatory molecules such as B7-1 (CD80) and B7-2 (CD86) that are related membrane-bound molecules. In view of the demonstrated allelic specificity of MAM for MHC molecules it is also tempting to project that these polymorphisms may influence the outcome of the MAM/TLR interactions. A recent observation that has relevance to the potential role of MAM-like SAgs in human rheumatoid arthritis (RA) is that in preliminary studies transgenic mice bearing the HLA-DR and HLA-DQ alleles that predispose to RA develop a type 1 adaptive cytokine profile in response to MAM, whereas cells from MAM-injected mice bearing those alleles that protect against RA develop a type 2 cytokine profile.