The Journal of Immunology, 2002, 168: 1281-1285.
Copyright © 2002 by The American Association of Immunologists
C-Terminal Anchoring of a Peptide to Class II MHC Via the P10 Residue Is Compatible with a Peptide Bulge1
Maryam Yassai,
Amin Afsari,
Jason Garlie and
Jack Gorski2
Blood Research Institute, Blood Center of Southeastern Wisconsin, Milwaukee, WI 53201
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Abstract
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The binding of antigenic peptide to class II MHC is mediated by
hydrogen bonds between the MHC and the peptide, by salt bridges, and by
hydrophobic interactions. The latter are confined to a number of deeper
pockets within the peptide binding groove, and peptide side chains that
interact with these pockets are referred to as anchor residues. T cell
recognition involves solvent-accessible peptide residues along with
minor changes in MHC helical pitch induced by the anchor residues. In
class I MHC there is an added level of epitope complexity that results
from binding of longer peptides that bulge out into the
solvent-accessible, T cell contact area. Unlike class I MHC, class II
MHC does not bind peptides of discrete length, and the possibility of
peptide bulging has not been clearly addressed. A peptide derived from
position 24–37 of integrin 
3 can either bind or not
bind to the class II MHC molecule HLA DRB3*0101 based on a polymorphism
at the P9 anchor. We show that the loss of binding can be compensated
by changes at the P10 position. We propose that this could be an
example of a class II peptide bulge. Although not as efficient as P9
anchoring, the use of P10 as an anchor adds another possible mechanism
by which T cell epitopes can be generated in the class II presentation
system.
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Introduction
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The
recognition of MHC-bound peptide by the TCR lies at center of the
adaptive immune response. There are two series of interactions that are
required; the first is the binding of the peptide to the MHC and the
second is the recognition of novel epitopes revealed by this binding.
The nature of the peptide binding is restrained by the structure of the
MHC. Thus, the structure of the class I MHC allows for the binding of
short peptides whose N-terminal and C-terminal ends are anchored into
pockets located at each end of the peptide binding groove (see Ref.
1 for a recent review). Structural studies have indicated
that the portion of the peptide recognized by the T cell corresponds to
the central, solvent-exposed portion of the peptide (2).
Although the binding of the peptide may change the structure of the MHC
to a small extent, the major source of non-self epitopes to be
recognized by self-tolerant TCR is provided by the peptide side chains
that point into the solvent. An additional level of epitope complexity
arises from the binding of peptides of different lengths, with many of
the longer peptides being accommodated by a bulging of the central
portion of the peptide (3, 4, 5, 6, 7, 8).
Peptide binding to class II MHC differs from the binding to class I in
that the peptides are not constrained in size. There are major binding
pockets at each end of the peptide binding groove; however, the
position of the helices allows the peptide to exit at either end
(reviewed in Ref. 9). The central region of the binding
groove consists of three or four shallow pockets that are involved in
peptide binding interactions. A large portion of allelic specificity in
peptide binding is a function of the nature of these shallow pockets as
the polymorphism in the terminal pockets is relatively restricted. The
interactions in the central region can be sufficient to stabilize those
peptides that do not show extensive anchoring in the terminal regions
(10, 11). Thus, the current view of class II MHC
peptide interactions is one of a peptide lying in a relatively shallow
grove with multiple contacts across the entire extent of the peptide
binding groove. This view has not included the possibility of the
peptide bulging out from the groove as has been reported for class
I.
The most important peptide anchor residue is referred to as P1 (or i)
and the final anchor occurs at P9 (i + 8). The identification of
peptide anchors past P9 could be indicative of a peptide bulge. There
have been reports that peptides binding to HLA-DR1 can use P10 as an
anchor (12, 13). The human class II MHC molecule
HLA-DRw52a (DRB3*0101) has a peptide binding motif that includes a
primary hydrophobic anchor at P1 and another hydrophobic anchor at P9
(14). There is an allele-specific requirement for an
acidic group at P4. Using an HLA-DRw52a-binding peptide derived from
integrin 3, we explore the alternate use of a
hydrophobic anchor at P10 in lieu of P9. The results are interpreted in
the context of a peptide bulge between the anchors at P6/P7 and
P10.
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Materials and Methods
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Expression of recombinant soluble HLA-DRB3*0101 proteins
Soluble human class II HLA-DRB3*0101 proteins were generated in
Sf9 insect cells using a baculovirus expression system as described
(15). High Five cells grown in serum-free medium Excell
405 (JRH Biosciences, Lenexa, KS) supplemented with
L-glutamine were coinfected with recombinant DRAsol and
DRB3*0101sol viruses at a multiplicity of infection of 10 for each
virus. At 72 h postinfection, cells were removed and the culture
medium was concentrated 
10-fold and used for immunoaffinity
purification using immobilized anti-HLA-DR mAb, L243. HLA-DR
molecules were eluted as described (16) and concentrated
into PBS using Centricon-30 (Amicon, Beverly, MA). The
concentrations of purified HLA-DR proteins were determined by UV
absorbance at 280 nm using an extinction coefficient of 77,000
M-1 cm-1
(16).
Peptides
Peptides derived from amino acid residues 24–37 of integrin
3 are described in Table I
. These peptides were synthesized by
standard solid-phase methods, purified by HPLC, and confirmed by mass
spectrometry. The peptides were labeled with FITC at the N-terminal end
and purified by reversed-phase HPLC.
Peptide binding assays
A total of 10 nM purified soluble HLA-DRB3*0101 proteins were
used in 50 µl of binding mixtures with indicated amounts of labeled
and/or unlabeled peptides. The binding conditions were 37°C in PBS
with 1 mM EDTA, 1 mM PMSF, 0.1 mM iodoacetamide, and 3 mM
NaN3 at pH 5.5 for 18 h. The binding
mixtures were resolved on native PAGE using Bio-Rad (Hercules, CA)
minigel electrophoresis apparatus for the fast separation of bound from
unbound peptides. The binding of FITC-labeled peptides was detected and
quantitated by ImageQuant software of FluorImager 575 (Molecular
Dynamics, Sunnyvale, CA) after electrophoresis. Control binding assays
included in all experiments were as follows: a reaction without HLA-DR
to check for possible peptide migration in the HLA-DR region, and the
PLG peptide to provide a positive control.
Visualization/modeling
To view possible peptide structures the DR3:class II-associated
invariant chain peptide
(CLIP)3 crystal structure
(17) was used as a basis for further modeling. HLA-DR and
peptide residues were modified to generate a DRw52a sequence with the
3 (residues 24–37) peptide in the binding
groove using Sybyl (Tripos, St. Louis, MO). The first step was to
change the -chain residues from DR3 to DRw52a (nine replacements)
and change the CLIP residues to those of the 3
(residues 24–37) peptide (11 of 12 residues replaced). The proline
inserted in the peptide at P8 was in trans, which is the
same conformation that was observed in the CLIP peptide. Energy
minimization was performed to eliminate incompatible geometries using
the default parameters of the Sybyl "Minimize" command and no
electrostatics. This was used as the base model. Two alternate
possibilities were modeled. In the first, the Leu at P9
(Leu33) was converted to Pro
(trans) and the Gly at P10 to Leu followed by
minimization. In the second, a Pro was inserted in
trans between P8 and P9 and the structure was minimized.
Files were saved in PDB format and visualized using Sybyl.
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Results
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Loss of peptide binding due to changes at the P9 anchor can be
partially offset by P10 modification
The peptide derived from region 24–37 of integrin
3, AWCSDEALPLGSPR, implicated in the response
to the platelet alloantigen
IIb3, has been shown
to bind to DRw52a (DRB3*0101). As part of this previous analysis
(14) a motif for DRw52a was defined as an
aromatic/hydrophobic P1 residue, Trp25, an acidic
P4 residue, Asp28, and a hydrophobic P9 residue,
Leu33. A truncated peptide starting at position
26, Cys, was unable to compete for binding, defining the P1 residue. A
peptide from an allelic form of integrin
3, wherein Leu33 is
changed to Pro, would not compete for binding to DRw52a. The acidic P4
residue was defined by sequence alignment. This motif has been
substantiated by others (18).
While testing a number of Pro33 peptides modified
at other positions, it was observed that substituting
Gly34 (P10) by Leu would restore a low level of
binding to DRw52a. The peptides used in these studies are described in
Table I
and will be referred to by a three-letter code defining the
residues present at positions 32–34. To examine the effect of this
substitution at P10 in more detail, a peptide binding experiment was
performed using identical aliquots of DRw52a and increasing amounts of
labeled peptide. The result of such an experiment is shown in Fig. 1. The binding of the PLG peptide is
shown in Fig. 1A and the lack of binding of the PPG peptide
is shown in Fig. 1B. The binding of the PPL peptide, in
which Gly34 has been replaced by Leu, is shown in
Fig. 1C. As can be observed, the PPL peptide is capable of
binding to DRw52a, although with a reduced level of efficiency compared
with the PLG peptide. The data were plotted to compare the levels of
binding of the different peptides (Fig. 2). The binding of the PPL peptide was
4-fold less than that for the PLG peptide.
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FIGURE 2. Plot of peptide binding data. The data from Fig. 1 are shown plotted as
relative fluorescence units (rfu) for each concentration. The relative
fluorescence data in the peaks were transferred from the FluorImager to
an Excel spreadsheet and plotted directly without fitting. Sources of
data points are identified in the legend.
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The P33L34 peptide can inhibit the binding of L33G34 to DRw52a
As a further check on the binding of the PPL peptide to DRw52a, a
competition binding assay was performed (Fig. 3). The ability of unlabeled PPL to
compete with the binding of labeled PLG was compared with the ability
of unlabeled PLG to compete with the labeled peptide. The results
indicate that PPL is a good competitor of the binding interaction.
These data are in relatively good agreement with the direct binding
assay and indicate a similar mode of binding for the two peptides.
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FIGURE 3. Plot of peptide competition results. The binding of labeled PLG peptide
was performed in the presence of increasing concentrations of the
peptide identified in the legend.
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L34 facilitates peptide binding in the absence of Pro at
position 33
The occurrence of a proline residue at P9 might play a role in the
ability of the P10 residue to function as an anchor. It is possible
that a proline can introduce a kink in the peptide structure that might
favor a P10 interaction with the peptide binding groove. The role of
proline at position 33 was investigated by modifying this position.
After testing a number of residues with smaller side chains, it was
observed that a peptide with glycine at the P9 position, PGG, showed
minimal binding to DRw52a. To determine whether the substitution of
leucine at the P10 will also anchor a peptide with Gly at position 33,
the binding of the PGG peptide was compared with that of the PGL
peptide. The results (Fig. 4) show that
there is an 8-fold increase in the binding of the PGL peptide over the
PGG peptide. However, it should be noted that the levels of binding
achieved are lower than those with Pro at position 33. Using equivalent
amounts of DRw52a, the PPL peptide binds over 4-fold better than does
the PGL peptide (Fig. 4D); thus, there appears to be an
effect of the proline in allowing for P10 anchoring.
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FIGURE 4. Binding of peptides with glycine at position P9. A,
Native PAGE of binding experiments for the PGG peptide.
B, Native PAGE of PGL binding. C, Plot of
binding curves for PGG and PGL. D, Plot of binding
curves of PLG and PPL peptides performed at the same time. The PPL
peptide is better at binding than PGL but, as expected, binds at
20% of the PLG peptide.
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The effect of Leu at P10 is not due to use of a different peptide
binding register
One trivial explanation of the binding of the
Pro33/Leu34 peptide is the
use of an alternate peptide register. The only possible alternate
register would be
AWCSDEALPPL,
with Cys and Glu acting as the P1 and P4 anchors. To show that the Leu
at position 34 was acting in the original register, we eliminated the
two side chains in question, substituting the Cys with Lys and the Glu
with Gln, and assayed the ability of the resulting peptide to bind to
DRw52a (Fig. 5). This peptide, K26Q29PPL,
which does not have the required hydrophobic and acidic residues at P1
and P4 in an alternate register, also bound to DRw52a (Fig. 5, lane 1). As expected, the binding was stronger with the
K26Q29PLL peptide (Fig. 5, lane 2). It should be pointed out
that these peptides also have Y substituted for W at the P1 anchor
(Table I) with no adverse effect.
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FIGURE 5. Native PAGE of peptide binding using peptides modified to eliminate any
possibility of alternate registers. Lane 1, K26Q29PPL
peptide; lane 2, K26Q29PLL peptide; lane
3, PLG peptide. The two K26Q29 peptides also have a Y for W
substitution at 25 (P1). Peptides concentration was 1 µm in the
binding assays.
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L34 facilitates peptide binding in the absence of Pro at
position 32
To further understand the effect of other peptide side chains on
the ability of the P10 residue to recapture binding, we determined
whether there is a requirement for a Pro at position 32. As described
earlier for position 33, proline may play a unique role in the ability
of P10 to anchor a peptide. Therefore, peptides with either Ala or Pro
at 32, Pro at 33 and Leu at 34 were tested for binding to HLA-DRw52a. A
Pro at position 32 was not required for the recovery of binding
observed initially with the PPL peptide, as equivalent concentrations
of the APL peptide and the PPL peptide bound with the same efficiency
(Fig. 6).
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FIGURE 6. Role of proline at position 32 on P10-mediated binding. Native PAGE
analysis of peptides with substitutions at position 32 (P8). Side
chains at each position are identified above the lanes. Peptide
concentrations were at 1 µm in the binding reactions. The results of
two independent binding experiments are shown for the PPL and APL
peptides. A PLG peptide-binding experiment was performed as a positive
control.
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Discussion
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The experiments described in this report indicate that a
hydrophobic side chain at P10 can partially reconstitute the loss of
binding of a peptide when the P9 anchor residue is substituted by Pro
or Gly. The pocket generated at the C-terminal end of the binding
groove is, in general, the second most profound pocket and thus would
be expected to contribute to the overall stability of a bound peptide.
There are two possible interpretations of this observation that differ
in the presumed geometry of the bound peptide. In the first of these,
the side chain at P10 acts at an independent site on the edge of the
peptide binding groove to compensate for the loss of the P9 anchor. In
the second, the residue at P10 interacts with the pocket that is
normally occupied by P9, resulting in a partially bulged peptide.
To help visualize these possibilities and to insure that structural
integrity was maintained, we modeled these possibilities. The x-ray
crystal structure of DR3 was used to generate the DRw52a structure by
replacement. Simultaneously, the peptide residues were changed from
those of the CLIP peptide, originally bound to the DR3, to those of the
3 integrin with Leu at 33. Energy minimization
without electrostatics was performed to eliminate incompatible
geometries. The Trp in the 3 sequence was
replaced by Tyr in the primary anchor position. A peptide with a Tyr
replacement works as well as the Trp peptide and shows the same P10
effect (Fig. 5 and data not shown). The orientation of the peptide is
shown in Fig. 7B.
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FIGURE 7. Model of peptides bound to HLA-DRw52a. A, P33L34 in
extended form. B, L33G34 in extended form.
C, P33L34 with L34 extending into the P9 pocket.
D, Overlay of all three structures. The peptide
positions are identified. P7 is pointing out of the plane of the paper.
P8, P9, and P10 show the largest displacement for form C (blue). Arrows
pointing up show positions of the P1 and P9 pockets.
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In the first model, the peptide backbone is left in its original
position and the side chains at P9 and P10 are simply exchanged for Pro
and Leu. In this manner, the aliphatic P10 residue would provide an
additional interaction with the class II MHC, anchoring the peptide
close to the outside of the binding groove. The resulting peptide
geometry (Fig. 7A) is compared with the model for the
original 3 peptide (Fig. 7B), in
which Leu33 is an anchor extending into the
nonpolar pocket (Fig. 7B, second arrow pointing
up).
There are two examples of class II structures in which this pocket is
not used by the bound peptide, which would be compatible with the first
model. In both cases there is a Gly at P9 and the pocket is empty of
other side chains. For I-Ag7-bound hen egg
lysozyme (19), the glycine participates in a number
of hydrogen bonds and the P10 residue, Tyr, closes the C-terminal end
of the peptide binding groove. For DR4-bound collagen II
(20), the Gly is also H-bonded, but the Leu at position 10
appears to be solvent exposed. Thus, I-Ag7-bound
hen egg lysozyme could be considered an example of the model. It
is also interesting to note that DRw52a and I-Ag7
are both examples of class II molecules in which the Asp57 to
Arg76 salt bridge is missing due to a polymorphism at 57.
The alternative model (Fig. 7C) was generated by inserting a
Pro between P8 and P9 of the 3 peptide, thus
maintaining the Leu anchor, which is now the P10 side chain. Because of
the additional Pro residue there is a strain introduced on the peptide
backbone, which is partly relieved by bulging and in part by allowing
the P10 side chain to slip out of the pocket to some extent. The two
prolines fill the groove, and the side chain at 32 bulges up slightly.
The three peptide structures are overlapped to show the putative
"bulge" structure that would result with the second possible
geometry (Fig. 7D). This level of modeling provides an
approximation of the possible actual structures, eliminating those
disfavored on basic steric grounds.
It is possible that the third structure would provide a greater chance
of stabilizing peptide binding. In this model, the position of
Leu31 (P7), which extends into a side pocket
under the ridge of the -chain helix, is maintained. A large part
of the hydrogen bonding between the peptide and the MHC would also be
maintained. Those disruptions that take place occur in the C-terminal
portion of the peptide, which may be less influential than if they took
place in the N-terminal portion (21). The relatively
conserved 69Asn H bonding to P8 is affected as the amino group of P9
is not available for bonding. The distance between the 69Asn amide
nitrogen and the carboxyl group of P7 has increased due to the kink and
bulge. The 67Arg and 61Trp H bonds are maintained. It should be
pointed out that the DR2-myelin basic protein structure showed that
peptide binding could be maintained without hydrogen bonding in the
C-terminal half of the peptide (11). The Val polymorphism
at 57 in DRw52a precludes that side chain from participating in
hydrogen bonding or forming the 57-76 salt bridge. This
polymorphism might result in a larger P9 pocket, as has been observed
for I-Ag7 (19, 22). A certain degree
of flexibility in the use of the pocket that normally binds the P9 side
chain has been shown in the case of I-Ag7-bound
GAD221–235 (Ref. 39 cited in 22). In this case Gly is the
P9 residue but the P9 pocket is occupied by a side chain from an
adjacent molecule in the crystal lattice (22). It will be
of great interest to determine the actual structure of a peptide-MHC
complex in which the P10 residue is implicated in stabilizing
binding.
The P10 residue, also referred to as i + 9, has been implicated in
providing peptide-anchoring function in HLA-DR1 (12, 13)
and HLA-DR2a (DRB5*0101) (11). In the case of DR1 it was
shown that a polyalanine helix with hydrophobic anchors at P1 and P10
were sufficient to result in high-affinity binding (12).
In the case of the DR2a, moving the P10 anchor side chain to P9
increased the binding of the peptide. The authors also modeled a
possible kink in the peptide backbone (23). However, the
role of P10 in antigenic peptides is not yet fully appreciated. We
demonstrate in this study that DRw52a also shows this characteristic,
indicating that P10 anchoring may be a general phenomenon for many if
not all class II alleles. It will be interesting to determine whether
certain class II alleles or isotypes can anchor peptides sufficiently
at both C and N termini to allow the much larger bulges that have been
reported for class I.
We provide direct data that the elimination of peptide binding by
changing the side chain of an anchor residue can be compensated for by
an additional change in a neighboring peptide side chain. We interpret
these results to indicate that by flexing the peptide, the neighboring
side chain can interact with the MHC pocket with sufficient efficiency
for maintaining the binding of the peptide. This would result in a
local perturbation of the peptide, in part resembling the bulges
described for class I peptide binding. It can be envisioned that
certain peptides will have the ability to use both the P9 and P10
residues for anchoring. In such cases, there exists the possibility of
generating two conformational epitopes from the same peptide-MHC
complex. It would be likely that T cells would distinguish the
difference between the two conformations, thus increasing the
immunogenicity of such a peptide.
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Acknowledgments
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We thank Drs. Larry Stern, Craig Beeson, and Ian Wilson for
discussion.
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Footnotes
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1 This work was supported by National Institutes of Health Grant RO1 AI26085. 
2 Address correspondence and reprint requests to Dr. Jack Gorski, Blood Research Institute, Blood Center of Southeastern Wisconsin, P.O. Box 2178, Milwaukee, WI 53201-2178. E-mail address: jack{at}bcsew.edu
3 Abbreviation used in this paper: CLIP, class II-associated invariant chain peptide.
Received for publication September 13, 2001.
Accepted for publication November 29, 2001.
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References
|
|---|
-
Natarjan, K., H. Li, R. A. Mariuzza, D. H. Margulies. 1999. MHC class I molecules, structure and function. Rev. Immunogen. 1:32.[Medline]
-
Garcia, K. C., L. Teyton, I. A. Wilson. 1999. Structural basis of T cell recognition. Annu. Rev. Immunol. 17:369.[Medline]
-
Guo, H. C., T. S. Jardetzky, T. P. Garrett, W. S. Lane, J. L. Strominger, D. C. Wiley. 1992. Different length peptides bind to HLA-Aw68 similarly at their ends but bulge out in the middle. Nature 360:364.[Medline]
-
Fremont, D. H., M. Matsumura, E. A. Stura, P. A. Peterson, I. A. Wilson. 1992. Crystal structures of two viral peptides in complex with murine MHC class I H-2Kb. Science 257:919.[Abstract/Free Full Text]
-
Madden, D. R., D. N. Garboczi, D. C. Wiley. 1993. The antigenic identity of peptide-MHC complexes: a comparison of the conformations of five viral peptides presented by HLA-A2. Cell 75:693.[Medline]
-
Achour, A., K. Persson, R. A. Harris, J. Sundback, C. L. Sentman, Y. Lindqvist, G. Schneider, K. Karre. 1998. The crystal structure of H-2Dd MHC class I complexed with the HIV-1-derived peptide P18–I10 at 2.4 Å resolution: implications for T cell and NK cell recognition. Immunity 9:199.[Medline]
-
Li, H., K. Natarajan, E. L. Malchiodi, D. H. Margulies, R. A. Mariuzza. 1998. Three-dimensional structure of H-2Dd complexed with an immunodominant peptide from human immunodeficiency virus envelope glycoprotein 120. J. Mol. Biol. 283:179.[Medline]
-
Speir, J. A., J. Stevens, E. Joly, G. W. Butcher, I. A. Wilson. 2001. Two different, highly exposed, bulged structures for an unusually long peptide bound to rat MHC class I RT1-Aa. Immunity 14:81.[Medline]
-
Nelson, C. A., D. H. Fremont. 1999. Structural principles of MHC class II antigen presentation. Rev. Immunogenet. 1:47.[Medline]
-
Scott, C.A., P. A. Peterson, L. Teyton, I. A. Wilson. 1998. Crystal structures of two I-Ad-peptide complexes reveal that high affinity can be achieved without large anchor residues. Immunity 8:319.[Medline]
-
Smith, K. J., J. Pyrdol, L. Gauthier, D. C. Wiley, K. W. Wucherpfennig. 1998. Crystal structure of HLA-DR2 (DRA*0101, DRB1*1501) complexed with a peptide from human myelin basic protein. J. Exp. Med. 188:1511.[Abstract/Free Full Text]
-
Kropshofer, H., H. Max, C. A. Muller, F. Hesse, S. Stevanovic, G. Jung, H. Kalbacher. 1992. Self-peptide released from class II HLA-DR1 exhibits a hydrophobic two-residue contact motif. J. Exp. Med. 175:1799.[Abstract/Free Full Text]
-
Fleckenstein, B., H. Kalbacher, C. P. Muller, D. Stoll, T. Halder, G. Jung, K. H. Wiesmuller. 1996. New ligands binding to the human leukocyte antigen class II molecule DRB1*0101 based on the activity pattern of an undecapeptide library. Eur. J. Biochem. 240:71.[Medline]
-
Wu, S., K. Maslanka, J. Gorski. 1997. An integrin polymorphism that defines reactivity with alloantibodies generates an anchor for MHC class II peptide binding: a model for unidirectional alloimmune responses. J. Immunol. 158:3221.[Abstract]
-
Wu, S., J. Gorski. 1996. The MHC class II-associated invariant chain-derived peptide clip binds to the peptide-binding groove of class II molecules. Mol. Immunol. 33:371.[Medline]
-
Gorga, J. C., V. Horejsi, D. R. Johnson, R. Raghupathy, J. L. Strominger. 1987. Purification and characterization of class II histocompatibility antigens from a homozygous human B cell line. J. Biol. Chem. 262:16087.[Abstract/Free Full Text]
-
Ghosh, P., M. Amaya, E. Mellins, D. C. Wiley. 1995. The structure of an intermediate in class II MHC maturation: CLIP bound to HLA-DR3. Nature 378:457.[Medline]
-
Nagvekar, N., L. Corlett, L. W. Jacobson, H. Matsuo, R. Chalkley, P. C. Driscoll, S. Deshpande, E. G. Spack, N. Willcox. 1999. Scanning a DRB3*0101 (DR52a)-restricted epitope cross-presented by DR3: overlapping natural and artificial determinants in the human acetylcholine receptor. J. Immunol. 162:4079.[Abstract/Free Full Text]
-
Latek, R. R., A. Suri, S. J. Petzold, C. A. Nelson, O. Kanagawa, E. R. Unanue, D. H. Fremont. 2000. Structural basis of peptide binding and presentation by the type I diabetes-associated MHC class II molecule of NOD mice. Immunity 12:699.[Medline]
-
Dessen. A., C. M., S. Lawrence, D. M. Cupo, D. M. Zaller, D. C. Wiley. 1997. X-ray crystal structure of HLA-DR4 (DRA*0101, DRB1*0401) complexed with a peptide from human collagen II. Immunity 7:473.[Medline]
-
McFarland, B. J., J. F. Katz, C. Beeson, A. J. Sant. 2001. Energetic asymmetry among hydrogen bonds in MHC class II-peptide complexes. Proc. Natl. Acad. Sci. USA 98:9231.[Abstract/Free Full Text]
-
Corper, A. L., T. Stratmann, V. Apostolopoulos, C. A. Scott, K. C. Garcia, A. S. Kang, I. A. Wilson, L. Teyton. 2000. A structural framework for deciphering the link between I-Ag7 and autoimmune diabetes. Science 288:505.[Abstract/Free Full Text]
-
Jurcevic, S., P. J. Travers, A. Hills, J. N. Agrewala, C. Moreno, J. Ivanyi. 1996. Distinct conformations of a peptide bound to HLA-DR1 or DRB5*0101 suggested by molecular modelling. Int. Immunol. 8:1807.[Abstract/Free Full Text]
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Abstract
Introduction
