Year: 2002
Type: conference-abstract
Abstract: The t-cell receptor (tcr) is a heterodimeric glycoprotein expressed on the surface of t lymphocytes that plays a central role in the recognition of foreign antigens from microbial pathogens or transformed cells in the context of the major histocompatibility complex (mhc).The ability to discriminate between self and foreign antigens resides in the fine specificity of the tcr interaction with mhc.We have determined crystal structures of the murine class i tcr 2c bound to self and non-self agonist peptides, and compared them with other murine and human class i and class ii tcr-pmhc complexes.The tcrs all dock onto their respective pmhc in a similar, diagonal orientation, but with variable contacts that provide specificity to the bound peptide and individual mhc.Conformational changes in the central cdr loops of the tcr facilitate the dual recognition of self (syngeneic) and foreign (allogeneic) mhc complexes.These tcr-pmhc structures have begun to probe the molecular mechanisms of alloreactivity, cross-reactivity, graft rejection, positive and negative selection, and autoimmunity.The range of antigens presented by mhc or mhc-like molecules has recently been extended to include large bulged peptides, glycopeptides, lipids, and glycolipids.Thus, the tcr can interact with a much broader diversity of microbial and self-antigens than was previously anticipated.Thus, the adaptive immune systems can respond not only to tumor antigens or foreign proteins from microbial pathogens, but also to non-protein components from the cell walls of mycobacteria, such as tuberculosis and leprosy.
Author: I. A. Wilson
Institution: Scripps Research Institute
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W2053108067