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1.
Kiley Prilliman Mark Lindsey Y. Zuo Ken W. Jackson Ying Zhang W. Hildebrand 《Immunogenetics》1997,45(6):379-385
A peptide-based vaccine must be bound and presented by major histocompatibility complex class I molecules to elicit a CD8+ T-cell response. Because class I HLA molecules are highly polymorphic, it has yet to be established how well a vaccine peptide
that stimulates one individual’s CD8+ cytotoxic T lymphocytes will be presented by a second individual’s different class I molecules. Therefore, to facilitate
precise comparisons of class I peptide binding overlaps, we uniquely combined hollow-fiber bioreactors and mass spectrometry
to assign precise peptide binding signatures to individual class I HLA molecules. In applying this strategy to HLA-B*1501, we isolated milligram quantities of B*1501-bound peptides and mapped them using mass spectrometry. Repeated analyses consistently assign the same peptide binding
signature to B*1501; the degree of peptide binding overlap between any two class I molecules can thus be determined through comparison of
their peptide signatures.
Received: 3 October 1996 / Revised: 20 November 1996 相似文献
2.
Kelly L. Arnett W. Huang Nicholas M. Valiante Linda D. Barber P. Parham 《Immunogenetics》1998,48(1):56-61
HLA-B*0801 is unique among HLA-B allotypes in having dominant amino acid anchors at positions 3 and 5 of the peptide-binding motif.
HLA-B*0802 is a variant of HLA-B*0801 in which the Bw6 sequence motif is replaced by a Bw4 sequence motif. This change, involving substitutions at positions
77, 80, 81, 82, and 83 of the B*08 heavy chain, is probably the result of a single evolutionary event of interallelic conversion. Moreover, the difference
between B*0802 and B*0801 is sufficient to stimulate a cytotoxic T-cell response. To assess further the functional impact of the Bw4 motif on a
B8 background, we compared the peptide-binding specificity of the B*0801 and B*0802 allotypes by sequencing the mixture of peptides endogenously bound to B*0802 and 12 individual peptides purified from that mixture. The HLA-B*0802 allotype, while able to bind some peptides bound by B*0801, has a broader repertoire of endogenously bound peptides than B*0801: the peptides bound by B*0802 are more variable in length and exhibit greater diversity in the carboxyl-terminal amino acid which interacts with the
F pocket.
Received: 29 October 1997 相似文献
3.
Nobuyuki Tanigaki Doriana Fruci Eliana Vigneti Giuseppe Starace Paolo Rovero Marco Londei Richard H. Butler Roberto Tosi 《Immunogenetics》1994,40(3):192-198
Five HLA-B27 subtypes, B*2701, B*2703, B*2704, B*2705, and B*2706, were tested for direct binding with twenty-six synthetic nonapeptides carrying the primary anchor residue motifs (combination of amino residues at positions 2 and 9) relevant to B*2705. The peptide sequences were derived from human HSP89, P53 and MBP. The alpha chains were immunospecifically isolated from LH (B
*
2701), CH (B
*
2703), WE1 (B
*
2704), BTB (B
*
2705), and LIE (B
*
2706) cells and their peptide binding was measured by the HLA class I alpha chain refolding assay. The data obtained indicated that the B27 subtypes tested can bind a common set of peptides carrying several different anchor residue motifs. The motifs, R-K and R-R, reported for B*2705 and a new motif H-R were accepted by B*2703, B*2704, and B*2706, but not by B*2701. However, other motifs, including known B*2702 and/or B*2705 motifs, R-H, R-L, R-A, and R-F, and a new motif found here, R-G, were apparently accepted by all B27 subtypes tested. The observed cross-peptide binding in the B27 subgroup is compatible with the so-called arthritogenic peptide hypothesis in the pathogenesis of ankylosing spondylitis. 相似文献
4.
K R Prilliman K W Jackson M Lindsey J Wang D Crawford W H Hildebrand 《Journal of immunology (Baltimore, Md. : 1950)》1999,162(12):7277-7284
Therapies to elicit protective CTL require the selection of pathogen- and tumor-derived peptide ligands for presentation by MHC class I molecules. Edman sequencing of class I peptide pools generates "motifs" that indicate that nonameric ligands bearing conserved position 2 (P2) and P9 anchors provide the optimal search parameters for selecting immunogenic epitopes. To determine how well a motif represents its individual constituents, we used a hollow-fiber peptide production scheme followed by the mapping of endogenously processed class I peptide ligands through reverse-phase HPLC and mass spectrometry. Systematically mapping and characterizing ligands from B*1508, B*1501, B*1503, and B*1510 demonstrate that the peptides bound by these B15 allotypes i) vary in length from 7 to 12 residues, and ii) are more conserved at their C termini than their N-proximal P2 anchors. Comparative peptide mapping of these B15 allotypes further pinpoints endogenously processed ligands that bind to the allotypes B*1508, B*1501, and B*1503, but not B*1510. Overlapping peptide ligands are successful in binding to B*1501, B*1503, and B*1508 because these B15 allotypes share identical C-terminal anchoring pockets whereas B*1510 is divergent in the C-terminal pocket. Therefore, endogenous peptide loading into the B15 allotypes requires that a conserved C terminus be anchored in the appropriate specificity pocket while N-proximal anchors are more flexible in their location and sequence. Queries for overlapping and allele-specific peptide ligands may thus be contingent on a conserved C-terminal anchor. 相似文献
5.
Doriana Fruci Paolo Rovero Richard H. Butler Rosa Sorrentino Roberto Tosi Nobuyuki Tanigaki 《Immunogenetics》1993,38(1):41-46
Eight nonamer peptides that comply with the major anchor residue motifs (the combination of amino acid residues at positions 2 and 9), R-K and R-R, of HLA-B27 (B*2705)-binding peptides were synthesized and tested for their direct binding to HLA class I alpha chains by the HLA class I alpha chain refolding assay previously described. One was a known B27 (B*2705)-binding heat shock protein peptide, HSP89 (201–209), and the other seven were derived from the sequence of wild-type P53, a human tumor suppressor protein. A total of 36 HLA class I allospecificities were tested. HSP89 (201–209) and two P53 peptides, P53 (362–370) and P53 (378–386), all possessing the motif R-K, bound strongly to B27 (B*2705) alpha chains. A weak binding was seen for P53 (272–280) and P53 (334–342), both showing the motif R-R. Most of these B27-binding peptides were found to bind to A3 alpha chains as well. In addition, P53 (173–181) and P53 (334–342), both with the R-R motif, showed substantial binding with A31 alpha chains. All the peptides, carrying the motif R-K also showed weak binding with A31 alpha chains. The remaining two peptides, P53 (201–209) and P53 (282–290), with the motif R-R, did not show significant bininding with any of the alpha chains tested. This study demonstrates both the specificity of peptide binding to a given HLA allelic product and the occurence of cross-peptide-binding between the allelic products of different HLA loci.
Correspondence to: N. Tanigaki. 相似文献
6.
Pool sequencing of natural HLA-DR,DQ, and DP ligands reveals detailed peptide motifs,constraints of processing,and general rules 总被引:6,自引:6,他引:0
Kirsten Falk Olaf Rötzschke Stefan Stevanovíc Günther Jung Hans-Georg Rammensee 《Immunogenetics》1994,39(4):230-242
We have approached the problem of MHC class II ligand motifs by pool sequencing natural peptides eluted from HLA-DR, DQ, and DP molecules. The results indicate surprisingly clear patterns, although not quite as clear as with natural class I ligands. The most striking feature is a highly dominant Proline at position 2. We interpret this to be a consequence of aminopeptidase N-like activity in processing. Another general aspect is the existence of three to four hydrophobic or aromatic anchors, whereby the first and the last are separated by five to eight residues. The peptide motifs for HLA-DR1, DR5, DQ7, and DPw4 are allele-specific and differ by spacing and occupancy of anchors. The anchors tend to be flanked by clusters of charged residues, and small residues, especially Ala, are frequent in the motif centers. These detailed motifs allow one to interpret most previous (DR-) motifs as fitting one or more of the anchors or conserved clusters. The relative motif symmetry suggests the possibility of bidirectional binding of peptides in the class II groove. 相似文献
7.
Escobar H Crockett DK Reyes-Vargas E Baena A Rockwood AL Jensen PE Delgado JC 《Journal of immunology (Baltimore, Md. : 1950)》2008,181(7):4874-4882
The majority of >2000 HLA class I molecules can be clustered according to overlapping peptide binding specificities or motifs recognized by CD8(+) T cells. HLA class I motifs are classified based on the specificity of residues located in the P2 and the C-terminal positions of the peptide. However, it has been suggested that other positions might be relevant for peptide binding to HLA class I molecules and therefore be used for further characterization of HLA class I motifs. In this study we performed large-scale sequencing of endogenous peptides eluted from K562 cells (HLA class I null) made to express a single HLA molecule from HLA-B*3501, -B*3502, -B*3503, -B*3504, -B*3506, or -B*3508. Using sequence data from >1,000 peptides, we characterized novel peptide motifs that include dominant anchor residues extending to all positions in the peptide. The length distribution of HLA-B35-bound peptides included peptides of up to 15 residues. Remarkably, we determined that some peptides longer than 11 residues represented N-terminal-extended peptides containing an appropriate HLA-B35 peptide motif. These results provide evidence for the occurrence of endogenous N-terminal-extended peptide-HLA class I configurations. In addition, these results expand the knowledge about the identity of anchor positions in HLA class I-associated peptides that can be used for characterization of HLA class I motifs. 相似文献
8.
Binding of nonamer peptides to three HLA-B51 molecules which differ by a single amino acid substitution in the A-pocket 总被引:2,自引:2,他引:0
Akiko Kikuchi Takashi Sakaguchi Kiyoshi Miwa Yuji Takamiya Hans-Georg Rammensee Yutaro Kaneko Masafumi Takiguchi 《Immunogenetics》1996,43(5):268-276
The interaction between 9-mer peptides and HLA-B51 molecules was investigated by quantitative peptide binding assay using
RMA-S cell expressing human β2-microglobulin and HLA-B51 molecules. Of 147 chemically synthesized 9-mer peptides possessing
two anchor residues corresponding to the motif of HLA-B*5101 binding self-peptides, 27 paptides bound to HLA-B*5101 molecules. Pro and Ala at position 2 as well as Ile at position 9 were confirmed to be main anchor residues, while Gly
at position 2 as well as Val, Leu, and Met at position 9 were weak anchor residues for HLA-B*5101. The A-pocket is suspected to have a critical role in peptide binding to MHC class I molecules because this pocket corresponds
to the N-terminus of peptides and has a strong hydrogen bond formed by conserved Tyr residues. Further analysis of peptide
binding to HLA-B*5102 and B*5103 molecules showed that a single amino acid substitution of Tyor for His at residue 171(B*5102) and that of Gly for Trp at residue 167 (B*5103) has a minimum effect in HLA-B51-peptide binding. Since previous studies showed that some HLA-B51 alloreactive CTL clones
failed to kill the cells expressing HLA-B*5102 or HLA-B*5103, these results imply that the structural change of the A-pocket among HLA-B51 subtypes causes a critical conformational
change of the epitope for TCR recognition rather than influences the interaction between peptides and MHC class I molecules. 相似文献
9.
Hiroya Kobayashi Taku Kokubo Yusuke Abe Keisuke Sato Shoji Kimura Naoyuki Miyokawa Makoto Katagiri 《Immunogenetics》1996,44(5):366-371
The peptide motif of the HLA-DR53 (DRB4*0101) molecule, which is associated with autoimmune diseases including Vogt-Koyanagi-Harada’s syndrome, was determined by
peptide binding assay using human L plastin p581 – 595 peptide and its substituted analogues. L plastin p581 – 595 peptide
is one of the naturally processed peptides bound to HLA-DR9/DR53 (DRB1*0901/DRB4*0101) molecules. The binding affinity of each peptide to the HLA-DR53 molecule was measured by fluorescence intensity of biotinylated
peptides to L cell transfectants expressing HLA-DR53 molecules, followed by treatment with avidin-fluorescence. Binding of
biotinylated peptides to HLA-DR53 molecules was not inhibited by all single-alanine-substituted nonbiotinylated peptides,
indicating that the replaced position was important for binding to the HLA-DR53 moleule. The inhibitory motif is considered
to be an HLA-DR53-specific binding motif, composed of a positively charged residue (K) at position 1, a hydrophobic residue
(I) at position 4, positively charged residue (R or K) at position 8 or 9, and another hydrophobic residue (I) at position
10. This predicted motif is different from the binding motifs of other HLA-DR molecules.
Received: 29 April 1996 / Revised: 16 June 1996 相似文献
10.
Duyar H Dengjel J de Graaf KL Wiesmüller KH Stevanović S Weissert R 《Immunogenetics》2005,57(1-2):69-76
Experimental autoimmune encephalomyelitis induced with myelin proteins in DA and LEW.1AV1 rats is a model of multiple sclerosis (MS). It reproduces major aspects of this detrimental disease of the central nervous system. MS is associated with the HLA-DRB1*1501, DRB5*0101, and DQB1*0602 haplotype. DA and LEW.1AV1 rats share the RT1av1 haplotype. So far, no MHC class II peptide motif of RT1.Da molecules has been described. Sequence alignment of the chain of the rat MHC class II molecule RT1.Da with human HLA class II molecules revealed strong similarity in the peptide-binding groove of RT1.Da and HLA-DRB1*1501. According to the putative peptide-binding pockets of RT1.Da, after comparison with the pockets of HLA-DRB1*1501, we predicted the peptide motif of RT1.Da. To verify the predicted motif, naturally processed peptides were eluted by acidic treatment from immunoaffinity-purified RT1.Da molecules of lymphoid tissue of DA rats and subsequently analyzed by ESI tandem mass spectrometry. In addition, we performed binding studies with combinatorial nonapeptide libraries to purified RT1.Da molecules. Based on these studies we could define a peptide-binding motif for RT1.Da characterized by aliphatic amino acid residues (L, I, V, M) and of F for the peptide pocket P1, aromatic residues (F, Y, W) for P4, basic residues (K, R) for P6, aliphatic residues (I, L, V) for P7, and aromatic residues (F, Y, W) and L for P9. Both methods revealed similar binding characteristics for peptides to RT1.Da. This data will allow epitope predictions for analysis of peptides, relevant for experimental autoimmune diseases. 相似文献
11.
H. Kobayashi T. Kokubo Michinari Takahashi Keisuke Sato Naoyuki Miyokawa Shoji Kimura Reiko Kinouchi Makoto Katagiri 《Immunogenetics》1998,47(5):398-403
Human T-cell-mediated autoimmune diseases are often genetically linked to particular alleles of HLA class II genes. Vogt-Koyanagi-Harada’s (VKH) disease, which is regarded as an autoimmune disorder in multiple organs containing
melanocytes, has been found to be associated with HLA-DR4 (DRB1*0405) and HLA-DR53 (DRB4*0101). Tyrosinase is a melanoma antigen (Ag) expressed by normal melanocytes as well as melanoma cells against which responses
by autologous T cells have been detected. We established a T-cell line from the peripheral blood of a patient with VKH disease
which responded to synthetic peptides corresponding to tyrosinase. The T-cell line was generated which recognized the tyrosinase
p188 – 208 peptide when presented by the HLA-DR4 (DRB1*0405) molecule on the surface of HLA class II-expressing L-cell transfectants. The minimal antigenic peptide which induced
T-cell responses was an 11-amino-acid sequence and located at tyrosinase p193 – 203 (E-I-W-R-D-I-D-F-A-H-E). This peptide
contained the DRB1*0405-binding peptide motif (hydrophobic residues (Y, F, W) at position 1 as an anchor residue, and negatively charged residues
(D, E) at position 9), which corresponded to the W at p195 and the D at p203. These observations demonstrate that tyrosinase
peptides are immunogenic, and may be a candidate for an autoantigen in VKH disease, suggesting that probing the T-cell responses
against synthetic peptides is a productive approach for identifying the autoantigenic peptides associated with autoimmune
diseases including VKH disease.
Received: 22 August 1997 / Revised: 7 October 1997 相似文献
12.
Unlike HLA-A and HLA-B, few peptide epitope motifs have been reported for HLA-C molecules. However, a number of cytotoxic T-lymphocyte epitopes derived from tumor antigens that bind to HLA-C molecules have been described. Here we report peptide-binding motifs for both HLA-Cw6.02 and HLA-Cw7.01 molecules. Recombinant human HLA molecules were generated and used to screen combinatorial 9mer peptide libraries. Complexes of HLA molecules properly folded and associated with 2-microglobulin and peptides were identified using a conformation-specific HLA class I antibody conjugated to alkaline phosphatase. In the presence of substrate, peptide beads can be readily isolated and microsequenced to determine peptide identity. Of the peptides that bound to HLA-Cw6.02 and HLA-Cw7.01, 19 and 18 peptides, respectively, were sequenced, allowing motif identification for each C allele. This is the first report of an HLA-Cw7.01 peptide motif and extends the findings of Falk et al. [(1993) Proc Natl Acad Sci USA 90:12005] for an HLA-Cw6.02 motif. Anchoring amino acids for the HLA-Cw6.02 motif were phenylalanine or tyrosine in position (P)1, arginine in P2, and an aliphatic/aromatic residue at P9. Anchoring residues for HLA-Cw7.01 were positively charged amino acids in P1 and P2. Unlike most other HLA molecules, we were unable to assign P9 an anchoring residue, and we suspect that HLA-Cw7.01 binds peptides in an unconventional manner. Additionally, preferred amino acids were identified for both molecules. Identification of HLA-Cw6.02 and HLA-Cw7.01 peptide-binding motifs makes a significant contribution to the C allele peptide-binding motifs and will allow investigators to predict, design, and test HLA-Cw6.02 and HLA-Cw7.01 engineered peptides for immunotherapy. 相似文献
13.
Elena Lorente Susana Infantes David Abia Eilon Barnea Ilan Beer Ruth García Fátima Lasala Mercedes Jiménez Carmen Mir Antonio Morreale Arie Admon Daniel López 《The Journal of biological chemistry》2012,287(42):34895-34903
The transporter associated with antigen processing (TAP) enables the flow of viral peptides generated in the cytosol by the proteasome and other proteases to the endoplasmic reticulum, where they complex with nascent human leukocyte antigen (HLA) class I. Later, these peptide-HLA class I complexes can be recognized by CD8+ lymphocytes. Cancerous cells and infected cells in which TAP is blocked, as well as individuals with unusable TAP complexes, are able to present peptides on HLA class I by generating them through TAP-independent processing pathways. Here, we identify a physiologically processed HLA-E ligand derived from the D8L protein in TAP-deficient vaccinia virus-infected cells. This natural high affinity HLA-E class I ligand uses alternative interactions to the anchor motifs previously described to be presented on nonclassical HLA class I molecules. This octameric peptide was also presented on HLA-Cw1 with similar binding affinity on both classical and nonclassical class I molecules. In addition, this viral peptide inhibits HLA-E-mediated cytolysis by natural killer cells. Comparison between the amino acid sequences of the presenting HLA-E and HLA-Cw1 alleles revealed a shared structural motif in both HLA class molecules, which could be related to their observed similar cross-reactivity affinities. This motif consists of several residues located on the floor of the peptide-binding site. These data expand the role of HLA-E as an antigen-presenting molecule. 相似文献
14.
15.
Colin Butter Karen Staines Andrew van Hateren T. Fred Davison Jim Kaufman 《Immunogenetics》2013,65(8):609-618
In contrast to typical mammals, the chicken MHC (the BF-BL region of the B locus) has strong genetic associations with resistance and susceptibility to infectious pathogens as well as responses to vaccines. We have shown that the chicken MHC encodes a single dominantly expressed class I molecule whose peptide-binding motifs can determine resistance to viral pathogens, such as Rous sarcoma virus and Marek’s disease virus. In this report, we examine the response to a molecular defined vaccine, fp-IBD1, which consists of a fowlpox virus vector carrying the VP2 gene of infectious bursal disease virus (IBDV) fused with β-galactosidase. We vaccinated parental lines and two backcross families with fp-IBD1, challenged with the virulent IBDV strain F52/70, and measured damage to the bursa. We found that the MHC haplotype B15 from line 15I confers no protection, whereas B2 from line 61 and B12 from line C determine protection, although another locus from line 61 was also important. Using our peptide motifs, we found that many more peptides from VP2 were predicted to bind to the dominantly expressed class I molecule BF2*1201 than BF2*1501. Moreover, most of the peptides predicted to bind BF2*1201 did in fact bind, while none bound BF2*1501. Using peptide vaccination, we identified one B12 peptide that conferred protection to challenge, as assessed by bursal damage and viremia. Thus, we show the strong genetic association of the chicken MHC to a T cell vaccine can be explained by peptide presentation by the single dominantly expressed class I molecule. 相似文献
16.
Akihiro Kondo John Sidney Scott Southwood Marie-France del Guercio Ettore Appella Hiroshi Sakamoto Howard M. Grey Esteban Celis Robert W. Chesnut Ralph T. Kubo A. Sette 《Immunogenetics》1997,45(4):249-258
Previous studies have defined two different peptide binding motifs specific for HLA-A
*
0101. These motifs are characterized by the presence of tyrosine (Y) at the C-termini of 9-mer and 10-mer peptides, and either
a small polar or hydrophobic (S, T, M) residue in position 2, or a negatively charged (D or E) residue in position 3. In this
study, the structural requirements for peptide binding to A
*
0101 have been further analyzed by examining the binding capacity of large sets of peptides corresponding to naturally occurring
sequences which bore one or the other of these two A
*
0101-specific motifs. By correlating the presence of specific residue types at each position along the peptide sequence with increased
(or decreased) binding affinity, the prominent influence of secondary anchor residues was revealed. In most cases, the two
anchors in positions 2 and 3 appear to act synergistically. With the exception of the DE3 submotif in 9-mer peptides, a positive role for aromatic residues in position 1 and the center of the peptide (positions
4 or 5 of 9- or 10-mer peptides, respectively), and proline at C-3, were also consistently detected. However, secondary anchor
residues also appear to differ significantly between the two different submotifs, demonstrating that A
*
0101 can utilize alternative modes in binding its peptide ligands. According to these analyses, specific refined submotifs were
also established, and their merit verified by independent sets of potential A
*
0101 binding peptides. Besides providing useful insight into the nature of the interaction of the A
*
0101 allele with its peptide ligands, such refined motifs should also facilitate accurate prediction of potential A
*
0101-restricted peptide epitopes.
Received: 16 July 1996 / Revised: 18 September 1996 相似文献
17.
Position 45 represents a highly polymorphic residue within HLA class I alleles, which contacts the p2 position of bound peptides
in 85% of the peptide–HLA structures analyzed, while the neighboring residues 41 and 46 are not involved in peptide binding.
To investigate the influence of residue 45 at the functional level, we sequenced peptides eluted from recombinant HLA-B*44:0841Ala/45Met/46Ala molecules and compared their features with known peptides from B*44:0241Thr/45Lys/46Glu. While HLA-B*44:02 has an anchor motif of E at the p2 anchor position, HLA-B*44:08 exhibits Q and L as anchor motif. The
45Met/Lys polymorphism contributes to the alteration in the peptide-binding motif and provides further evidence that mismatches at
position 45 should be considered as nonpermissive in a transplantation setting. 相似文献
18.
H. Kubo Y. Ikeda-Moore A. Kikuchi Kiyoshi Miwa Kiyoshi Nokihara Christian Schönbach M. Takiguchi 《Immunogenetics》1998,47(3):256-263
HLA-B*3501 and -B*5101 molecules, which belong to the HLA-B5 cross-reactive group, bind peptides carrying similar anchor residues at P2 and
the C-terminus, but differences are observed in the preference for a Tyr residue at the C-terminus and the affinity of peptides.
A recent study of HLA-B*3501 crystal structure suggested that residue 116 on the floor of the F-pocket determines a preference for anchor residues
at the C-terminus. In order to evaluate the role of the residue 116 in the peptide binding to both HLA-B*3501 and HLA-B*5101 molecules, we generated HLA-B*3501 mutant molecules carrying Tyr at residue 116 (B*3501–116Y) and tested the binding of a panel of nonamer peptides to the B*3501–116Y molecules by a stabilization assay with RMA-S transfectants expressing the mutant molecules. The substitution of
Tyr for Ser at residue 116 markedly reduced the affinity of nonamer peptides carrying Tyr at P9, while it enhanced that of
nonamer peptides carrying Ile and Leu at P9. On the other hand, the affinity of peptides carrying aliphatic hydrophobic residues
at P9 to B*3501–116Y molecules was much higher than that to HLA-B*3501 and HLA-B*5101 molecules. These results indicate that residue 116 is critical for the structural difference of the F-pocket between
HLA-B*3501 and HLA-B*5101 which determines the C-terminal anchor residues, while leaving other residues which differ between HLA-B*3501 and HLA-B*5101 may be responsible for the low peptide binding property of the latter.
Received: 18 April 1997 / Revised: 18 September 1997 相似文献
19.
Y. van de Wal Yvonne M. C. Kooy Jan Wouter Drijfhout Reinout Amons George K. Papadopoulos Frits Koning 《Immunogenetics》1997,46(6):484-492
To understand the dominant association of celiac disease (CD) with the presence of HLA-DQ(α1*0501, β1*0201), the peptide binding characteristics of this molecule were compared with that of the structurally similar, but non-CD-associated
DQ(α1*0201, β1*0202) molecule. First, naturally processed peptides were acid-extracted from immuno-affinity-purified DQ molecules of both
types. Both molecules contained the Ii-derived CLIP sequence and a particular fragment of the major histocompatibility complex
(MHC) class I α chain. Use of truncated analogues of these two peptides in cell-free peptide binding assays indicated that
identical peptide frames are used for binding to the two DQ2 molecules. Detailed substitution analysis of the MHC class I
peptide revealed identical side chain requirements for the anchor residues at p6 and p7. At p1, p4, and p9, however, polar
substitutions (such as N, Q, G, S, and T) were less well tolerated in the case of the DQ(α1*0201, β1*0202) molecule. The most striking difference between the two DQ molecules is the presence of an additional anchor residue
at p3 for the DQ(α1*0201, β1*0202) molecule, whereas this residue was found not to be specifically involved in binding of peptides to DQ(α1*0501, β1*0201). Similar results were obtained applying substitution analysis of the CLIP sequence. Molecular modelling of the DQ2 proteins
complexed with the MHC class I and CLIP peptide corresponds well with the binding data. The results suggest that both CLIP
and the MHC class I peptide bind DQ(α1*0501, β1*0201) and DQ(α1*0201, β1*0202) in a DR-like fashion, following highly similar binding criteria. This detailed characterization of unique peptide binding
properties of the CD-associated DQ(α1*0501, β1*0201) molecule should be helpful in the identification of CD-inducing epitopes.
Received: 21 March 1997 / Revised: 28 May 1997 相似文献
20.
Masaaki Ibe Yuki Ikeda Moore Kiyoshi Miwa Yutaro Kaneko Shumpei Yokota Masafumi Takiguchi 《Immunogenetics》1996,44(4):233-241
The binding capacity of one-hundred-and-seventy-two 8-mer to 11-mer peptides carrying HLA-A24 anchor residues to HLA-A*2402 molecules was analyzed by using a HLA class I stabilization assay. Most (76.2%) of these peptides bound to HLA-A*2402 molecules. These results confirmed previous findings that Tyr and Phe at P2 as well as Phe, Trp, Ile, and Leu at the
C-terminus were main anchor residues for HLA-A*2402. Tyr at P2 was a stronger anchor residue than Phe, while bulky aromatic hydrophobic residues Phe and Trp at the C-terminus
are stronger anchors than aliphatic hydrophobic residues Ile and Leu. These results were also supported by an analysis using
a panel of mutated 9-mer peptides at P2 and P9. Taken together, these results suggest that HLA-A*2402 molecules have deep B- and F-pockets because they favor peptides carrying bulky aromatic hydrophobic residues at P2 and
the C-terminus. The affinity of 8-mer peptides was significantly lower than that of 9-mer to 11-mer peptides, while there
was no difference in affinity between 9-mer, 10-mer, and 11-mer peptides. The affinity of peptides carrying bulky aromatic
hydrophobic residues at the C-terminus was higher than that of peptides carrying aliphatic hydrophobic residues in each of
the 8-mer to 11-mer peptides, though the greatest difference in affinity was observed in 11-mer peptides. The strong interaction
of side chains of these anchor residues with the corresponding pockets may permit the effective binding of 10-mer and 11-mer
peptides to HLA-A*2402 molecules. 相似文献