Structural basis of CD8 coreceptor function revealed by crystallographic analysis of a murine CD8alphaalpha ectodomain fragment in complex with H-2Kb.
The crystal structure of the two immunoglobulin variable-like domains of the murine CD8alphaalpha homodimer complexed to the class I MHC H-2Kb molecule at 2.8 A resolution shows that CD8alphaalpha binds to the protruding MHC alpha3 domain loop in an antibody-like manner. Comparison of mouse CD8alphaalpha/H-2Kb and human CD8alphaalpha/HLA-A2 complexes reveals shared as well as species-specific recognition features. In both species, coreceptor function apparently involves the participation of CD8 dimer in a bidentate attachment to an MHC class I molecule in conjunction with a T cell receptor without discernable conformational alteration of the peptide or MHC antigen-presenting platform.
Kern
P S
PS
Laboratory of Immunobiology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Teng
M K
MK
Smolyar
A
A
Liu
J H
JH
Liu
J
J
Hussey
R E
RE
Spoerl
R
R
Chang
H C
HC
Reinherz
E L
EL
Wang
J H
JH
D000595:Amino Acid Sequence; D000818:Animals; D016827:CD8 Antigens / Q000737:chemistry* / Q000235:genetics; D018360:Crystallography, X-Ray; D019281:Dimerization; D006183:H-2 Antigens / Q000737:chemistry* / Q000235:genetics; D015789:HLA-A2 Antigen / Q000737:chemistry / Q000235:genetics; D006801:Humans; D046911:Macromolecular Substances; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics
D016827:CD8 Antigens; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D015789:HLA-A2 Antigen; D046911:Macromolecular Substances; D010446:Peptide Fragments; D011994:Recombinant Proteins