+検索条件
-Structure paper
タイトル | Structure of a fully assembled tumor-specific T cell receptor ligated by pMHC. |
---|---|
ジャーナル・号・ページ | Cell, Vol. 185, Issue 17, Page 3201-3213.e19, Year 2022 |
掲載日 | 2022年8月18日 |
著者 | Lukas Sušac / Mai T Vuong / Christoph Thomas / Sören von Bülow / Caitlin O'Brien-Ball / Ana Mafalda Santos / Ricardo A Fernandes / Gerhard Hummer / Robert Tampé / Simon J Davis / |
PubMed 要旨 | The T cell receptor (TCR) expressed by T lymphocytes initiates protective immune responses to pathogens and tumors. To explore the structural basis of how TCR signaling is initiated when the ...The T cell receptor (TCR) expressed by T lymphocytes initiates protective immune responses to pathogens and tumors. To explore the structural basis of how TCR signaling is initiated when the receptor binds to peptide-loaded major histocompatibility complex (pMHC) molecules, we used cryogenic electron microscopy to determine the structure of a tumor-reactive TCRαβ/CD3δγεζ complex bound to a melanoma-specific human class I pMHC at 3.08 Å resolution. The antigen-bound complex comprises 11 subunits stabilized by multivalent interactions across three structural layers, with clustered membrane-proximal cystines stabilizing the CD3-εδ and CD3-εγ heterodimers. Extra density sandwiched between transmembrane helices reveals the involvement of sterol lipids in TCR assembly. The geometry of the pMHC/TCR complex suggests that efficient TCR scanning of pMHC requires accurate pre-positioning of T cell and antigen-presenting cell membranes. Comparisons of the ligand-bound and unliganded receptors, along with molecular dynamics simulations, indicate that TCRs can be triggered in the absence of spontaneous structural rearrangements. |
リンク | Cell / PubMed:35985289 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.08 Å |
構造データ | EMDB-13427, PDB-7phr: |
化合物 | ChemComp-NAG: |
由来 |
|
キーワード | IMMUNE SYSTEM / T-cell receptor / TCR / Major Histocompatibility Complex / MHC / Antigen / Adaptive Immunity / Cancer / Complex |