Antigen Presenting Cells (APCs)
365
Fig. 4
X-ray structure of the MHC class I
molecule HLA-Aw68, the MHC class II
molecule HLA-DR1, and the CD1b molecule,
which are key surface molecules of APCs.
Adapted from Guo, H. C. et al. (1992)
Nature
26
, 300–301; Murthy, V. L., Stern, L. J. (1997)
Structure
5
, 1385–1396; Gadola, S. D.,
Zaccai, N. R., Harlos, K., Shepherd, D.,
Castro-Palomino, J. C., Ritter, G.,
Schmidt, R. R., Jones, E. Y. Cerundola, V.
(2002) Structure of human CD1b with bound
ligands at 2.3
˚
A, a maze for alkyl chains,
Nat.
Immunol
.
3
, 721–726.
MHC I
MHC II
CD1
a
1
a
1
a
1
a
2
a
3
b
2m
b
1
b
2
b
2m
a
2
a
2
a
3
of peptides being 9-mers; (2i) 1 to 2 side
chains of the peptide, called
anchors
,F
t
into corresponding speciFcity pockets in
the binding cleft. Both the position and
identity of these anchor residues vary, de-
pending on the particular MHC class I
molecule (allele-speciFc anchor motifs);
and (3) the amino- and carboxyterminni
of peptides are Fxed in the binding cleft
through a hydrogen-bonding network.
To illustrate this in more detail, the
sequences of self- and foreign peptides
restricted by the human MHC class I
molecule HLA-A2 are compared (Table 3):
70% of these peptides are 9-mers with
a leucine or methionine at the anchor
position P2 and a valine at the anchor
position P9. Owing to the fact that the
sequences at the nonanchor positions are
widely irrelevant for binding, more than
Tab. 3
Peptide anchor motif of antigenic peptides binding to the MHC class I molecules HLA-A1
and HLA-A2.
Antigen
Sequence
Allele
P2
P9
P10
Tyrosinase (369–377)
Y
M
NGTMSQ
V
EBV LMP2 (426–434)
C
L
GGLL TM
V
HIV RT(476–484)
I
L
KEPVHG
V
HTLV-1 Tax(11–19)
I
L
FG
YPVY
V
HLA-A2
Hepatitis B sAg(335–343)
W
L
SLLVPF
V
Tyrosinase (1–9)
M
M
NGTMSQ
V
pmel 17/gp100
I
L
DGTAT L
R
L
Influenza B NP(85–94)
K
L
GEFYNQM
M
Influenza MP(59–68)
I
L
GFVFTL T
V
HPV11 E7 (4–12)
R
L
VTLKDI
V
Anchor motif
LV
ML
M
Anchor motif
P3
P9
D
Y
HLA-A1
E
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