Abstract

T lymphocytes recognize a variety of foreign antigens through the cell-surface glycoproteins known as T cell receptors (TCRs). Recognition of peptide antigens presented by major histocompatibility complex (MHC) molecules is mediated by diverse (xp heterodimers of the TCR. The Voc and Vp domains of TCRs form the recognition surface for MHC/peptide complexes. In order to facilitate NMR studies of the V(xNp heterodimer, the Voc and Vp domains were expressed as a single polypeptide in E. coli. The solution structure of a single-chain T cell receptor (scTCR) derived from the MHC class II-restricted DIO TCR was determined using NMR spectroscopy. The scTCR is a 27.8 kD protein comprising 255 amino acids. The structure was determined using heteronuclear, multi-dimensional NMR spectroscopy using protein enriched in """"""""N, """"""""C and 2 H isotopes. The conformations of complementarity determining regions (CDRs) 3P and I a and surface properties of 2a are different from related class I-restricted TCRs. A conserved orientation for TCR Vadomains in complexes with both class I and II MHC/peptide ligands is inferred, implying that small structural variations in V(X confer MHC class preference. High mobility of CDR3 residues relative to other CDR or framework residues (picosecond timescale) provides insight into immune recognition and selection mechanisms. I

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR000995-25
Application #
6355144
Study Section
Project Start
2000-05-01
Project End
2001-04-30
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
25
Fiscal Year
2000
Total Cost
$1,070
Indirect Cost

  Institution

Name
Massachusetts Institute of Technology
Department
Type
DUNS #
City
Cambridge
State
MA
Country
United States
Zip Code
02139

  Publications

Marintchev, Assen; Edmonds, Katherine A; Marintcheva, Boriana et al. (2009) Topology and regulation of the human eIF4A/4G/4H helicase complex in translation initiation. Cell 136:447-60
Frueh, Dominique P; Arthanari, Haribabu; Koglin, Alexander et al. (2009) A double TROSY hNCAnH experiment for efficient assignment of large and challenging proteins. J Am Chem Soc 131:12880-1
Frueh, Dominique P; Leed, Alison; Arthanari, Haribabu et al. (2009) Time-shared HSQC-NOESY for accurate distance constraints measured at high-field in (15)N-(13)C-ILV methyl labeled proteins. J Biomol NMR 45:311-8
Lentz, Margaret R; Westmoreland, Susan V; Lee, Vallent et al. (2008) Metabolic markers of neuronal injury correlate with SIV CNS disease severity and inoculum in the macaque model of neuroAIDS. Magn Reson Med 59:475-84
Hyberts, Sven G; Heffron, Gregory J; Tarragona, Nestor G et al. (2007) Ultrahigh-resolution (1)H-(13)C HSQC spectra of metabolite mixtures using nonlinear sampling and forward maximum entropy reconstruction. J Am Chem Soc 129:5108-16
Chen, Jingyang; Dupradeau, Francois-Yves; Case, David A et al. (2007) Nuclear magnetic resonance structural studies and molecular modeling of duplex DNA containing normal and 4'-oxidized abasic sites. Biochemistry 46:3096-107
Lentz, Margaret R; Kim, John P; Westmoreland, Susan V et al. (2005) Quantitative neuropathologic correlates of changes in ratio of N-acetylaspartate to creatine in macaque brain. Radiology 235:461-8
Kim, John P; Lentz, Margaret R; Westmoreland, Susan V et al. (2005) Relationships between astrogliosis and 1H MR spectroscopic measures of brain choline/creatine and myo-inositol/creatine in a primate model. AJNR Am J Neuroradiol 26:752-9
Peled, S; Cory, D G; Raymond, S A et al. (1999) Water diffusion, T(2), and compartmentation in frog sciatic nerve. Magn Reson Med 42:911-8
Mo, H; Dai, Y; Pochapsky, S S et al. (1999) 1H, 13C and 15N NMR assignments for a carbon monoxide generating metalloenzyme from Klebsiella pneumoniae. J Biomol NMR 14:287-8

Showing the most recent 10 out of 12 publications