Trends in Immunology
Feature ReviewPresent Yourself! By MHC Class I and MHC Class II Molecules
Section snippets
Why Do We Need to Present Antigens?
T cells help eliminate pathogens present in infected cells and also help B cells make better and different kinds of antibodies to protect against extracellular microbes and toxic molecules. To accomplish these important functions, T cells have to interact intimately with other cells and then find and instruct or eliminate the ones that are harboring or have been exposed to these pathogenic threats. However, T cells are unable to peek beneath the surface of cells to identify ones that have
The MHC Scaffold, or How Did MHC I and MHC II Molecules Evolve?
MHC I and II molecules present protein fragments to CD8+ and CD4+ T cells, respectively. These molecules are essential for cell-mediated immunity and therefore appeared at the inception of the adaptive immune system 500 million years ago [1]. For their construction they used two immunoglobulin domains topped by two parallel alpha helixes resting on a platform of beta-pleated sheets. This capital structure generated a peptide-binding groove between the alpha helices 2, 3 that is, ‘evolutionarily
How to Present Your Inner Self? MHC Class I Molecules
MHC I molecules present peptides from the proteins that are synthesized by cells. In healthy cells, all of these proteins are autologous ones to which CD8+ T cells are tolerant. However, when cells are expressing mutant sequences (e.g., in cancers), microbial genes (e.g., from viral infections), or foreign polymorphic genes (e.g., from transplants), these ‘non-self’ antigenic peptides are included in the presented peptidome, allowing CD8+ T cells to detect and destroy these abnormal cells. How
MHC Class II Molecules
MHC II molecules are both similar and different from MHC I molecules, as are their mechanisms of presentation. MHC II molecules are expressed on immune cells such as B cells, monocytes, macrophages, and dendritic cells and on epithelial cells following inflammatory signals, while MHC I molecules are expressed more ubiquitously. MHC II molecules on dendritic cells present antigen to naïve CD4+ T cells to activate them; later MHC II molecules participate in the interaction of B cells and
Concluding Remarks and Future Perspectives
The work of many laboratories over past decades has informed our understanding of the function of MHC class I and MHC class II molecules at the immunological, cell biological, genetic, and atomic level. Many of the major mechanisms of both the MHC I and the MHC II pathways are understood and we can look forward to an even more comprehensive understanding of antigen presentation mechanisms in the coming years. With such knowledge, we can look forward to better understanding how these processes
Acknowledgments
This work was supported by grants from NWO-TOP and an ERC Advanced Grant to J.N. and NIH grants RO1AI114495 and RO1AI110374 to K.L.R.
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