Tolerance

The site of primary T-cell activation is a determinant of the balance between intrahepatic tolerance and immunity. Bowen, D. G. et al. J. Clin. Invest. 114, 701–712 (2004)

This study by Bertolino and colleagues provides an explanation for the fact that the liver can be both tolerogenic and immunogenic. Liver allografts can often be accepted across a complete MHC mismatch, and the liver is thought to have a role in oral tolerance. By contrast, immune responses to pathogens such as the hepatitis B and C viruses can occur in the liver. Recent studies have shown that the liver can be a site of primary CD8+ T-cell activation. These authors showed that hepatic versus lymph-node activation of naive CD8+ T cells determines whether tolerance or immunity develops to an antigen expressed in the liver. T-cell activation in the lymph nodes resulted in acute hepatitis, whereas activation in the liver led to inefficient function and reduced half-life of T cells.

T-cell responses

Upregulation of the CLIP self peptide on mature dendritic cells antagonizes T helper type 1 polarization. Rohn, T. A. et al. Nature Immunol. 5, 909–918 (2004).

Many studies have indicated that recognition of self-peptide–MHC complexes is involved in T-cell development, function and survival in both the thymus and the periphery. This study looked specifically at the role of class-II-associated invariant-chain peptide (CLIP)–MHC class II complexes, and it provides the first example of a self-peptide that regulates the activation of T cells specific for foreign antigen. The authors show that mature dendritic cells can upregulate expression of cell-surface CLIP–MHC class II complexes as a result of downregulation of HLA-DM activity (which would normally exchange CLIP for an exogenous antigen). The CLIP–MHC class II complexes are localized to immunological synapses with CD4+ T cells — together with MHC class II molecules carrying exogenous peptide — where they influence the type of T helper (TH)-cell response to the exogenous peptide by favouring TH2-cell polarization.

Structure

Crystal structure of a shark single-domain antibody V region in complex with lysozyme. Stanfield, R. L. et al. Science 19 August 2004 (doi:10.1126/science.1101148).

Cartilaginous fish such as the nurse shark are the oldest living organisms to have components of the adaptive immune system, but the relationship of these components to human antigen receptors is unclear. This paper reports the crystal structure of the nurse-shark immunoglobulin IgNAR bound to hen-egg lysozyme. Similar to camelid antibodies, IgNAR is a heavy-chain homodimer, with each IgNAR heavy chain consisting of one variable (V) domain and five constant (C) domains. However, the V domain of the IgNAR heavy chain clusters phylogenetically with the V regions of the T-cell receptor or immunoglobulin light chains, and this new structure will help to further our knowledge of the origins and evolution of the antigen receptors of the adaptive immune system.