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1.
Takashi Sakaguchi Masaaki Ibe Kiyoshi Miwa Yutaro Kaneko Shumpei Yokota Katsuaki Tanaka M. Takiguchi 《Immunogenetics》1997,45(4):259-265
The binding of 303 8-mer to 11-mer peptides carrying the anchor residues at P2 and the C-terminus to HLA-B*5101 molecules was examined by a stabilization assay in which peptides were incubated with RMA-S-B*5101 cells at 26 °C for 3 h. Analysis of the binding of these peptides to HLA-B*5101 molecules showed that Pro and Ala at P2, and Ile, Val, and Leu at the C-terminus functioned as anchor residues, while
Gly at P2 and Met at the C-terminus were weak anchors. Pro was a stronger anchor residue than Ala at P2, while Ile was the
strongest anchor at the C-terminus. Among 8-mer to 11-mer peptides, the 9-mer peptides showed the strongest binding to HLA-B*5101 molecules. This is in contrast to our recent findings that 10-mer and 11-mer peptides bind to HLA-B*3501 molecules as effectively as 9-mer peptides. Since both HLA class I molecules have the same B-pocket and the binding peptides
carry the same anchor residues, it is assumed that the structure of the F-pocket may restrict the length of binding peptides.
The ability of HLA-B*5101 binding peptides to stabilize the HLA-B*5101 molecules was markedly lower than that of HLA-B*3501 binding peptides to stabilize the HLA-B*3501 molecules. It is known that HLA-B*5101 is a slow assembling molecule, while HLA-B*3501 assembles rapidly. The results imply that the slow assembling of HLA-B*5101 molecules results from the low affinity of peptides to HLA-B*5101 molecules.
Received: 14 August 1996 / Revised: 8 October 1996 相似文献
2.
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
3.
T. Sakaguchi Y. Takamiya Michael Edidin Kiyoshi Nokihara Kiyoshi Miwa Christian Schönbach M. Takiguchi 《Immunogenetics》1997,47(2):149-158
The monoclonal antibody (mAb) 4D12 specific for the HLA-B5, -B35 cross-reacting group (CREG) bound to a fraction of HLA-B*3501 and HLA-B*5101 molecules carrying self-peptides. Analysis of the binding of mAb 4D12 to HLA-B*3501 and -B*5101 molecules pulsed with chemically synthesized peptides revealed that this mAb recognizes a restricted number of peptides
and that P1 of the bound peptides critically influences its binding. The 4D12 mAb bound only to HLA-B*3501 molecules carrying peptides with Asn, Asp, Glu, Ser, and Val at P1. Analysis using an HLA-B*3501 crystallographic model suggested that 4D12 may recognize the side chain of the P1 residue that is pointing to the solvent.
On the other hand, 4D12 bound only to HLA-B*5101 molecules carrying peptides with Asn or Asp at P1, suggesting that the 4D12 epitope formed by Glu, Ser, or Val at P1
and the A-pocket was changed by the substitution of His for Tyr at residue 171 of HLA-B*3501 molecules. This was confirmed by testing the binding of mAb 4D12 to HLA-B*3501 mutant molecules at residue 171 carrying these peptides. These results together suggest that the conformation of the
A-pocket and its hydrogen bound network with the P1 residue is also critical for the binding of mAb 4D12. The present study
shows the molecular basis of the specificity of 4D12 for the peptide-HLA class I complex.
Received: 19 June 1997 / Revised: 27 August 1997 相似文献
4.
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
5.
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
6.
C. A. McIntyre Robert C. Rees Kathryn E. Platts Catherine J. Cooke M. Olivia Smith Kevin A. Mulcahy Anna K. Murray 《Cancer immunology, immunotherapy : CII》1996,42(4):246-250
The MAGE gene family of tumour antigens are expressed in a wide variety of human cancers. We have identified 43 nonamer peptide sequences,
from MAGE-1, -2 and -3 proteins that contain binding motifs for HLA-A3 MHC class I molecules. The T2 cell line, transfected
with the cDNA for the HLA-A3 gene, was used in a MHC class I stabilisation assay performed at 37°C and 26°C. At 37°C, 2 peptides
were identified that stabilised HLA-A3 with high affinity (fluorescence ratio, FR >1.5), 4 peptides with low affinity (FR
1.11 – 1.49) and 31 peptides that did not stabilise this HLA haplotype (FR <1.1). At 26°C, 12 peptides were identified that
stabilised HLA-A3 with high affinity, 8 peptides with low affinity and 17 peptides that did not stabilise this HLA haplotype.
Two peptides stabilised HLA-A3 at both temperatures. Small changes in one to three amino acids at positions distinct from
the anchor residues altered peptide affinity. Data were compared to a similar study in which a peptide competition assay was
used to investigate MAGE-1 peptide binding to several HLA haplotypes. This study demonstrates that anchor residues do not
accurately predict peptide binding to specific HLA haplotypes, changes in one to three amino acids at positions distinct from
anchor residues influence peptide binding and alternative methods of determining peptide binding yield different results.
We are currently investigating the ability of these peptides to induce antitumour cytotoxic T lymphocyte activity as they
may be of potential therapeutic value.
Received: 4 January 1996 / Accepted: 20 March 1996 相似文献
7.
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
8.
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
9.
B. H. Johansen Tore Jensen Christopher J. Thorpe Frode Vartdal Erik Thorsby Ludvig M. Sollid 《Immunogenetics》1996,45(2):142-150
We compared the peptide binding specificity of three HLA-DQ molecules; HLA-DQ(α1*0501, β1*0201), HLA-DQ(α1*0201, β1*0202), and HLA-DQ(α1*0501, β1*0301). The first of these molecules confers susceptibility to celiac disease and insulin-dependent diabetes mellitus, while
the two latter molecules, which share either the α chain or the nearly identical β chain with HLA-DQ(α1*0501, β1*0201), do not predispose to these disorders. The binding of peptides was detected in biochemical binding assays as inhibition
of binding of radiolabeled indicator peptides to affinity-purified HLA-DQ molecules. Binding experiments with several peptides
demonstrated a clear difference in peptide binding specificity between the three HLA-DQ molecules. Further, single amino acid
substitution analyses indicated that the HLA-DQ molecules have different peptide binding motifs. The experimental data were
corroborated by computer modelling analysis. Our data suggest that the three HLA-DQ molecules prefer large hydrophobic residues
in P1 of peptides with subtle differences in side-chain preferences. HLA-DQ(α1*0501, β1*0201) and HLA-DQ(α1*0201, β1*0202) both prefer large hydrophobic residues in P9, whereas HLA-DQ(α1*0501, β1*0301) prefers much smaller residues in this position. HLA-DQ(α1*0501, β1*0201) and HLA-DQ(α1*0201, β1*0202), in contrast to HLA-DQ(α1*0501, β1*0301), prefer negatively charged residues in P4 and P7. A less prominent P6 pocket also appears to differ between the three
HLA-DQ molecules. Our results indicate that polymorphic residues of both the α and the β chain determine the peptide binding
specificity of HLA-DQ(α1*0501, β1*0201), but that the β chain polymorphisms appears to play the most important role. The information on peptide residues which
are advantageous and deleterious for binding to these HLA-DQ molecules may make possible the prediction of characteristic
features of peptide that bind to HLA-DQ(α1*0501, β1*0201) and precipitate celiac disease.
Received: 2 July 1996 / Revised: 7 August 1995 相似文献
10.
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
11.
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
12.
Eduardo Gómez-Casado G. Vargas-Alarcón Jorge Martinez-Laso Mercedes Perez-Blas Julio Granados Zulay Layrisse Fabiola Montoya Pilar Varela A. Arnaiz-Villena 《Immunogenetics》1997,46(6):469-476
HLA-B is the most polymorphic of the major histocompatibility complex classical class I loci. This polymorphism is mainly in exons
2 and 3, which code for the molecule’s α1 and α2 domains and include the antigenic peptide binding site. Recent studies have
indicated that not only exons but also the intron 2 region may be involved in the generation of certain HLA-B alleles such as B
*
3906 and B
*
1522. To study the degree of intron 2 participation and the mechanisms that generate polymorphism at the HLA-B locus, intron 1 and 2 sequences from the HLA-B35, -B5, -B16 and -B15 groups of alleles were obtained. A group-specific intronic
polymorphism was found: namely, B
*
5301 shows intron 1 and 2 sequences identical to those found in all B35 alleles studied. On the other hand, B
*
5101 and B
*
52012 show the same intron 1 and 2 sequences and their intron 1 is the same as that found in the B35 group. This suggests that B5 and B35 groups of alleles may have arisen from a common ancestor. All known B16 alleles show the same introns 1 and 2, with the exception of B
*
39061 and B
*
39062, and all B15 alleles also bear the same introns 1 and 2, with the exception of B
*
1522. Variability at intron 1 is more restricted than at intron 2, and the use of intron 1 for HLA-B allele phylogenetic analysis is better for grouping alleles of a postulated common origin. In conclusion, there is a remarkable
conservation of intronic sequences within related HLA-B alleles, which probably reflects a common origin and perhaps a selective force avoiding DNA changes. Intronic sequences are
also potentially useful to design DNA typing strategies.
Received: 11 March 1997 / Revised: 29 May 1997 相似文献
13.
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
14.
Amino acid and protein analyses have allowed the construction of a model for the C4-based Rodgers and Chido blood group antigens.
The single low-frequency allele (WH) in this blood group system, however, has not been characterized at the molecular level. Two WH+ donors were studied by C4 agarose gel electrophoreses, immunoblot studies using monoclonal anti-Rg: 1 or anti-Ch: 1, serological
phenotyping, polymerase chain reaction-restriction fragment length polymorphism of their C4 genes, and DNA sequencing of the WH allele. The first donor had the C4A1, A3 phenotype; the C4A1 carried Ch: 1, 3, 6 (thus exhibiting reversed antigenicity)
and the C4A3 carried the WH antigen. The amino acid sequence of the WH allele was PCPVLD at positions 1101 – 1106, S at position 1157, and VDLL at positions 1188 – 1191. A second donor typed as
C4A2, A4, B1 and was also WH+. Immunoblot analysis showed that a C4B1 protein expressed Rg: 1. Sequence analysis of the C4B genes showed the amino acids LSPVIH at positions 1101 – 1106, S at position 1157, and ADLR at positions 1188 – 1191. Thus,
the WH antigen is a conformational epitope that can arise through different mechanisms on either a C4A or C4B gene.
Received: 22 November 1995 / Revised: 19 February 1996 相似文献
15.
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
16.
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
17.
Chihiro Motozono John J. Miles Zafrul Hasan Hiroyuki Gatanaga Stanley C. Meribe David A. Price Shinichi Oka Andrew K. Sewell Takamasa Ueno 《PloS one》2013,8(6)
Antigen cross-reactivity is an inbuilt feature of the T cell compartment. However, little is known about the flexibility of T cell recognition in the context of genetically variable pathogens such as HIV-1. In this study, we used a combinatorial library containing 24 billion octamer peptides to characterize the cross-reactivity profiles of CD8+ T cells specific for the immunodominant HIV-1 subtype B Nef epitope VY8 (VPLRPMTY) presented by HLA-B*35∶01. In conjunction, we examined naturally occurring antigenic variations within the VY8 epitope. Sequence analysis of plasma viral RNA isolated from 336 HIV-1-infected individuals revealed variability at position (P) 3 and P8 of VY8; Phe at P8, but not Val at P3, was identified as an HLA-B*35∶01-associated polymorphism. VY8-specific T cells generated from several different HIV-1-infected patients showed unique and clonotype-dependent cross-reactivity footprints. Nonetheless, all T cells recognized both the index Leu and mutant Val at P3 equally well. In contrast, competitive titration assays revealed that the Tyr to Phe substitution at P8 reduced T cell recognition by 50–130 fold despite intact peptide binding to HLA-B*35∶01. These findings explain the preferential selection of Phe at the C-terminus of VY8 in HLA-B*35∶01+ individuals and demonstrate that HIV-1 can exploit the limitations of T cell recognition in vivo. 相似文献
18.
The ability to develop type II collagen (CII)-induced arthritis (CIA) in mice is associated with the major histocompatibility
I-A gene and with as yet poorly defined regulatory molecules of the major histocompatibility complex (MHC) class II antigen processing
and presentation pathway. H2-M molecules are thought to be involved in the loading of antigenic peptides into the MHC class
II binding cleft. We sequenced H2-Ma, H2-Mb1, and H2-Mb2 genes from CIA-susceptible and -resistant mouse strains and identified four different Ma and Mb2 alleles and three different Mb1 alleles defined by polymorphic residues within the predicted peptide binding groove. Most CIA-resistant mouse strains share
common Ma, Mb1, and Mb2 alleles. In contrast, H2-M alleles designated Ma-III, Ma-IV, Mb1-III, and Mb2-IV could be exclusively identified in the CIA-susceptible H2
r
and H2
q
haplotypes, suggesting that allelic H2-M molecules may modulate the composition of different CII peptides loaded onto MHC
class II molecules, presumably presenting “arthritogenic” epitopes to T lymphocytes.
Received: 8 December 1995 / Revised: 16 January 1996 相似文献
19.
P. Becker Azman Asmat Julaihi Mohamad Misli Moksin Melvin T. Tyree 《Trees - Structure and Function》1997,11(7):432-435
In contrast with previous reports, we observed high transpiration rates in mangrove trees. Maximum sap velocities and mean
daytime sap flow rates were estimated from heat pulse velocity in entire, field grown trees of Avicennia cf. alba Blume and Rhizophora apiculata Blume. Results were within the range of values measured by identical techniques for trees in lowland dipterocarp and tropical
heath forests with a similar climate in Brunei Darussalam (north Borneo). High stomatal conductance (400 mmol m –
2 s –
1) was also measured for well insolated leaves of A. cf. alba, with midday water potentials reaching about – 3 MPa in both species.
Received: 11 September 1996 / Accepted: 27 January 1997 相似文献
20.
Yvonne van de Wal Yvonne M. C. Kooy Jan Woulter Drijfhout Reinout Amons Frits Koning 《Immunogenetics》1996,44(4):246-253
Genetic susceptibility to coeliac disease (CD) is strongly associated with the expression of theHLA-DQ2 (α1*0501, β1*0201) allele. There is evidence that this DQ2 molecule plays a role in the pathogenesis of CD as a restriction element for
gliadin-specific T cells in the gut. However, it remains largely unclear which fragments of gliadin can actually be presented
by the disease-associated DQ dimer. With a view to identifying possible CD-inducing antigens, we studied the peptide binding
properties of DQ2. For this purpose, peptides bound to HLA-DQ2 were isolated and characterized. Dominant peptides were found
to be derived from two self-proteins: in addition to several sizevariants of the invariant chain (li)-derived CLIP peptide,
a relatively large amount of an major histocompatibility complex (MHC) class I-derived peptide was found. Analogues of this
naturally processed epitope (MHClα46–63) were tested in a cell-free peptide binding competition assay to investigate the requirements
for binding to DQ2. First, a core sequence of 10 amino acids within the MHClα46–63 peptide was identified. By subsequent single
amino acid substitution analysis of this core sequence, five putative anchor residues were identified at relative positions
P1, P4, P6, P7, and P9. Replacement by the large, positively charged Lys at these positions resulted in a dramatic loss of
binding. However, several other non-conservative substitutions had little or no discernable effect on the binding capacity
of the peptides.
Substitutions at P1 and P4 were most critical, suggesting a more prominent role as anchor residues. Structural features of
the DQ2 molecule that may relate to the binding motif and to gluten sensitivity are discussed. 相似文献