MHC TOOLS


Molecular Visualization of MHC Molecules

Use Rasmol or Chime to view these molecules on your own computer

Click here to download the following PDB coordinate files:
 

MHC II
Peptide
Resolution  (angstrom)
PDB Name
Date entered
DR1
Ha
3.8
1DLH
2/94
DR1
A2
2.4
1AQD
2/97
DR1 - SuperAg
mix
2.7
 1SEB
06/96
DR1 - TCR
Ha
2.6
 1FYT
11/00
DR2
MBP
2.6
1BX2
10/98
DR3
CLIP
2.8
1A6A
2/98
DR4-SEB
collag
2.5
2SEB
10/97
DR4
Ha
n.a
on hold
12/99
DR4
unnat. AA's
2.45
 1D5X
06/00
DR4
unnat. AA's
2.0
 1D5Z
06/00
DR4
unnat. AA's
2.45
 1D6E
06/00
DR4
unnat. AA's
2.0
 1D5M
06/00
IEk
Hb
2.3
1IEA
4/96
IEk
Hsp
2.7
1IEB
4/96
IAk
HEL
1.0
1IAK
11/97
IAd
Ova
2.6
1IAO
3/98
IAd
conalb
3.2
ID9K
10/99

Or  Click Here to view a Chime demonstration with your web browser (Netscape 4.0 or higher works best.  Chime Plug-In is Required)

MHC sequence data

MHC genes (HLA-DR, HLA_DQ, and HLA-DP) are the most polymorphic genes in the human genome

The nomeclature for MHC alleles can be a little alarming - click here for short introduction

Click  here for an alignment of some HLA-DR beta chain sequences

The current HLA database lists all known human alleles with good  search and display tools (courtesy of the IMGT  project)

The clustalw plot at right shows the relationship between HLA-DR alleles  PDF file


 larger version    pdf
Peptide binding motifs
 
MHC proteins have allele-specific peptide binding  preferences, called motifs 

HLA-DR1, our favorite MHC protein, exhibits side chain preferences at positions 1,4,6,9 
position 1:  Trp,Tyr,Phe > Met, Leu, Ile, Val 
position 4:   Met, Gln, Leu 
position 6:  Gly,Pro,Ala,Ser 
position 9:  hydrophobic 

Note that these match the positions of pockets observed in the structure as seen at right

There are several prediction programs available which give binding scores for different peptide binding registers in a sequence.

1:  EpiPred by Thomas Cameron
Excel spreadsheets which analyze many alleles according to algorithms of Hammer/Sinigaglia, A. Sette, and the Virtual Matrices of Sturniolo and
Hammer, limited to peptides of lenth 1000 aa.  **NOTE: this must be run in Internet Explorer.

2:  TEPITOPE, available from J. Hammer at his non-profit company Vaccinome predicting epitopes according to the Virtual Matrices of Sturniolo and Hammer.

3: ProPred, by Harpreet Singh, sponsored by the Bioinformatics
Centre (BIC) at the Institute of Microbial Technology in Chandigarh, India which predicts epitope peptides based on the Virtual matrices of Struniolo and Hammer. This has a nice graphical format for its output.

4: SYFPEITHI uses matrices which are described in a recent book by HG Rammensee et al.

5: Epipredict uses matrices developed primarily by B. Fleckenstein and K.-H Wiesmüller.

Try several to see which you prefer.


MHC tetramers
Tetramers formed by complexing biotinylated MHC proteins to streptavidin have generated a lot of interest, and have potential uses to select T-cells with a particular specificity. Linking multiple MHC proteins together increases their avidity for T-cells.

Follow this link to a .pdf file with tetramer staining protocols

Follow this link to the Tetramer Facility 

(courtesy of NIAID)


Follow this link for HLA Sequence Data
This site provides nucleotide and protein sequences for nearly all HLA genes 
(courtesy of the Anthony Nolan Bone Marrow Trust) 
 

MHC Procedures
Follow this link to a list of .pdf files with many protocols and procedures from Tom Cameron.

Links: