2v2w

File:2v2w.gif

spinqualitylabelsall models 2v2w, resolution 1.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

T CELL CROSS-REACTIVITY AND CONFORMATIONAL CHANGES DURING TCR ENGAGEMENT

OverviewOverview

All thymically selected T cells are inherently cross-reactive, yet many, data indicate a fine specificity in antigen recognition, which enables, virus escape from immune control by mutation in infections such as the, human immunodeficiency virus (HIV). To address this paradox, we analyzed, the fine specificity of T cells recognizing a human histocompatibility, leukocyte antigen (HLA)-A2-restricted, strongly immunodominant, HIV gag, epitope (SLFNTVATL). The majority of 171 variant peptides tested bound, HLA-A2, but only one third were recognized. Surprisingly, one recognized, variant (SLYNTVATL) showed marked differences in structure when bound to, HLA-A2. T cell receptor (TCR) recognition of variants of these two, peptides implied that they adopted the same conformation in the, TCR-peptide-major histocompatibility complex (MHC) complex. However, the, on-rate kinetics of TCR binding were identical, implying that, conformational changes at the TCR-peptide-MHC binding interface occur, after an initial permissive antigen contact. These findings have, implications for the rational design of vaccines targeting viruses with, unstable genomes.

DiseaseDisease

Known diseases associated with this structure: Abacavir hypersensitivity, susceptibility to OMIM:[142800], Ankylosing spondylitis, susceptibility to, 1 OMIM:[142800], Hypoproteinemia, hypercatabolic OMIM:[109700], Stevens-Johnson syndrome, susceptibility to OMIM:[142800]

About this StructureAbout this Structure

2V2W is a Protein complex structure of sequences from Homo sapiens. This structure superseeds the now removed PDB entry 2BSU. Full crystallographic information is available from OCA.

ReferenceReference

T cell cross-reactivity and conformational changes during TCR engagement., Lee JK, Stewart-Jones G, Dong T, Harlos K, Di Gleria K, Dorrell L, Douek DC, van der Merwe PA, Jones EY, McMichael AJ, J Exp Med. 2004 Dec 6;200(11):1455-66. PMID:15583017

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