Receptors on cytotoxic T lymphocytes and natural killer cells play well-established roles in the immunological response and share a common ligand in the form of MHC-I. We discuss how a variety of MHC-I receptors are also expressed on myelomonocytic cells such as macrophages and dendritic cells. Since myelomonocytic MHC-I receptors recognise a broad range of alleles and MHC-I structures, we propose that their task is to discern expression levels and folding forms of MHC. We describe a model in which these recognition events would regulate bidirectional cross talk between cells of innate and adaptive immune systems to organise an ongoing combined immune response. We discuss how such a model is supported by recent literature and might function in a variety of contexts, including immunoregulation during pregnancy. Our model also offers an alternative explanation of immune dysregulation rather than autoimmunity during HLA-B27-associated spondyloarthropathies and addresses a number of conundrums in this field. BioEssays 27: 542-550, 2005. (c) 2005 Wiley periodicals, Inc.
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