Recognition of self-peptide-MHC complexes by autoimmune T-cell receptors.
T cell receptors (TCR) recognize antigenic peptides displayed by MHC molecules. Whereas T-cell recognition of foreign peptides is essential for immune defense against microbial pathogens, recognition of self-peptides can cause autoimmune disease. Structural studies of anti-foreign TCR showed remarkable similarities in the topology of TCR binding to peptide-MHC, which maximize interactions with the ligand. However, recent structures involving autoimmune and tumor-specific TCR have revealed that they engage self-peptide-MHC with different topologies, which are suboptimal for TCR binding. These differences might reflect the distinct selection pressures exerted on anti-microbial versus autoreactive T cells. The structures also provide new insights into TCR cross-reactivity, which can contribute to autoimmunity by increasing the likelihood of self-peptide-MHC recognition.
Deng
Lu
L
Center for Advanced Research in Biotechnology, W.M. Keck Laboratory for Structural Biology, University of Maryland Biotechnology Institute, Rockville, MD 20850, USA.
Mariuzza
Roy A
RA
D000818:Animals; D015551:Autoimmunity; D003429:Cross Reactions; D006801:Humans; D008285:Major Histocompatibility Complex / Q000276:immunology*; D051379:Mice; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*
D010455:Peptides; D011948:Receptors, Antigen, T-Cell