共查询到20条相似文献,搜索用时 218 毫秒
1.
Yoshiki Miyachi Siew-Lin Wee Li-Kuang Chen F.Carl Grumet Robert J. Bowman Joel D. Taurog 《Human immunology》1984,10(4):237-249
A cytolytic human T cell (CTL) clone, designated F/M-F159, has been produced, the lytic specificity of which distinguishes subtypes of HLA-B27. This was demonstrated in cell-mediated lympholysis (CML) assays of: 1) a panel of target cells from unrelated donors, 75 B27 + and 36 B27−; 2) six families, including 20 B27+ and 14 B27− individuals; and 3) B27+ and B27− variants of a B27+ lymphoblastoid cell line (LCL). Specificity of F/M-F159 for HLA-B27 was confirmed by blocking studies with monoclonal antibodies. Lysis of B27+ targets reactive with the anti-B27 monoclonal antibody B27M2 was 30–104%, while lysis of B27+,B27M2− targets was 4–22%. Lysis of B27- targets expressing HLA-Bw47, known to be cross-reactive with the B27M2 antibody, was 10 to 19%, while lysis of all other B27 - targets was 10%. Clone F/M-F159 lysed B27+ targets, and failed to lyse B27-targets, irrespective of the clinical status of the cell donors. It is concluded that F/M-F159 recognizes an epitope present on the majority of serologically identified HLA-B27 molecules and that this epitope is close related to, but not identical with, the epitope recognized by the antibody B27M2. These findings are interpreted as supporting a direct role for HLA-B27 in disease pathogenesis. 相似文献
2.
A monoclonal antibody that binds specifically to HLA-B27, B7, and B22 is described. Binding to B27 appeared to be slightly stronger than to B7 and stronger than to B22 in an indirect binding assay, but no difference in B7 and B27 binding could be detected by Scatchard analysis. No distinction could be made between B27 on cells from normal and from ankylosing spondylitis patients in any assay system. The antibody, which was not cytotoxic, blocked complement-dependent cytolysis mediated by human HLA typing sera specific for B7 and B27. Competitive binding studies with other monoclonal antibodies showed that ME1 could block the binding of antibodies that recognized different antigenic sites on HLA. ME1 did not bind to Klebsiella pneumoniae. This reagent will be useful in further analysis of the relationship between B27 and ankylosing spondylitis. 相似文献
3.
I. L. MACLEAN S. IQBALL P. WOO A. C. S. KEAT R. A. HUGHES G. H. KINGSLEYJ S. C. KNIGHT 《Clinical and experimental immunology》1993,91(2):214-219
The spondartliropathy (Sp)-associated HLA-B27 antigen includes al least seven subtypes. B*2701–07, of which 01, 02, 05 and 07 occur in Caucasians. This study examined the B27 subtype distribution in British patients with Sp. The 133 HLA-B27+ subjecis comprised 94 European Caucasian Sp (58 ankylosing spondylitis (AS), 22 reactive arlhrilis (ReA: 11 sexually acquired (SARA). 11 enteric (EReA)). eight undifferentiated Sp (USp). and six pauciarticular juvenile-onset chronic arthritis (pJCA)) patients, antl 34 healthy Caucasian controls, together with four Asian Indian and one Chinese. 35S-labelled B27 was immunoprecipitated with anti-B27 MoAbs. and subtyped according to isoelectric point (pi) following isoelectric focussing. The use of B27 MoAb permitted subtype assignment without full class 1 HLA lyping. The vast majority (95%) were B*27O5 (Caucasian controls 31/34; AS 55/58; ReA 21/22; USp 8/8. and pJCA 6/6; Indian control 1/1 and AS 2/3: Chinese pJCA I/I), and the remainder B*2702. No B*270l or 07 subjects were identified. AS occurs in both B*2702 and 05 subjects, and we extend this observation to small numbers of ReA and of Indian AS subjects. This implicates molecular features shared between B27 subtypes, rather than subtype-determining regions of the antigen, in Sp palhogenesis. 相似文献
4.
A. Wölpl A. Toubert K. Siemoneit T. H. Eiermann H. Neumayer S. F. Goldmann 《Tissue antigens》1995,46(4):305-312
Abstract: We describe here the generation and characterization of two human monoclonal IgM antibodies (UL-4F11 and UL-F6) reactive with HLA-B27. The monoclonal antibody (mAb) UL-4F11 is cytotoxic for peripheral mononuclear cells and, therefore, useful as typing reagent for HLA-B27 and HLA-B38. Protein chemistry showed that the mAb UL-4F11 precipitates HLA-B27 molecules. Epitope mapping analysis suggests that the amino acids 45, 67, 82 and 83 (alpha-1 domain) of the HLA-B27 sequence are necessary for mAb UL-4F11 reactivity. The mAb UL-F6 is suitable for complement dependent lysis of lymphoblastoid cell lines and stimulated peripheral blood mononuclear cells with HLA-B27 (B*2701, B*2702, B*2703, B*2705, B*2707), B13, B40 (60, 61), B47 and B48 specificities. Its reactivity indicates that the amino acid valine in position 152 and glutamic acid in position 163 of the alpha-2 domain are crucial for the binding epitope. 相似文献
5.
ObjectiveEndoplasmic reticulum (ER) aminopeptidase 1 (ERAP1) variants contribute to the risk of ankylosing spondylitis in HLA-B27 positive individuals, implying a disease-related interaction between these gene products. The aim of this study was to determine whether reduced ERAP1 expression would alter the cell surface expression of HLA-B27 and the formation of aberrant disulfide-linked forms that have been implicated in the pathogenesis of spondyloarthritis.MethodsERAP1 expression was knocked down in monocytic U937 cells expressing HLA-B27 and endogenous HLA class I. The effect of ERAP1 knockdown on the accumulation HLA-B alleles (B18, B51, and B27) was assessed using immunoprecipitation, isoelectric focusing, and immunoblotting, as well as flow cytometry with antibodies specific for different forms of HLA-B27. Cell surface expression of aberrant disulfide-linked HLA-B27 dimers was assessed by immunoprecipitation and electrophoresis on non-reducing polyacrylamide gels.ResultsERAP1 knockdown increased the accumulation of HLA-B27 on the cell surface including disulfide-linked dimers, but had no effect on levels of HLA-B18 or -B51. Antibodies with unique specificity for HLA-B27 confirmed increased cell surface expression of complexes shown previously to contain long peptides. IFN-γ treatment resulted in striking increases in the expression of disulfide-linked HLA-B27 heavy chains, even in cells with normal ERAP1 expression.ConclusionsOur results suggest that normal levels of ERAP1 reduce the accumulation of aberrant and disulfide-linked forms of HLA-B27 in monocytes, and thus help to maintain the integrity of cell surface HLA-B27 complexes. 相似文献
6.
Peter Parham 《Human immunology》1985,12(4):213-221
A hybrid mouse monoclonal IgGl having one low affinity combining site for HLA-A2 and one low affinity combining site for HLA-B7 was made by the chemical method of Nisonoff and Palmer (Science 143:376,1964). This involved selective reduction of interchain disulphides, a splitting of the IgGl into half molecules at low pH and ionic strength, and reassociation of the half molecules by neutralization. Serologically active hybrids were separated from parental IgGl by an absorbtion procedure and recovered in about 10% yield. The hybrid discriminated between cells that express either HLA-A2 of HLA-B7 from cells that express both A2 and B7. This is because it could bind bivalently to the cell with both A2 and B7 but could only bind with a single combining site to cells expressing A2 or B7. The consequence of these different modes of attachment was to give up to sevenfold greater binding to the cell expressing A2 and B7 in comparison to the cell expressing only A2 or B7. 相似文献
7.
Bernard Frangoulis Murielle Reboul Anna Rocca Marika Pla 《European journal of immunology》1993,23(2):338-342
A set of mouse HLA-B27-reactive cytotoxic T lymphocyte clones were found to recognize the HLA-B27 molecule in an H-2-unrestricted manner, i.e. independently of any mouse major histocompatibility complex (MHC) molecule. The reactivity patterns of these clones on HLA-B27 variants (positive only on HLA-B*2702 and HLA-B*2701) allowed the identification of residues N77 and A81 of the HLA-B27 molecule as important for their reactivity. The location of these residues in the peptide-binding groove (specificity pocket F) suggested that the reactivity of the clones is dependent on HLA-B27-bound peptide(s). However, several other class I molecules sharing these residues (N77 and A81) were not recognized, indicating that other residues might also be involved. One of the clones was found to display an interesting cross-reactivity with allogeneic H-2Kk molecules, sharing N77 and A81 with HLA-B*2702. Sequence comparison suggested the involvement of residue H9, located in specificity pocket B of the peptide-binding groove, and revealed some similarity of pockets B in HLA-B27 and H-2Kk. The structural basis of such T cell-mediated MHC cross-reactions across species barriers is discussed. 相似文献
8.
A monoclonal antibody, MHM.5, specific for HLA class I antigens, bound to lymphocytes of all donors tested and was thought to bind to a monomorphic determinant. When the antibody was used to precipitate 35S methionine labeled HLA class I molecules from lymphoid cells, which were then isoelectric focused, it was found that the HLA-A1,A2 and A3 antigens were not precipitated. Similarly, MHM.5, which is IgG1, failed to block complement mediated lysis by alloantisera specific for HLA-A1, 2 and 3, and most other HLA-A antigens. HLA-Aw24, A25, and A32, and all other HLA-B and C typing reactions tested were blocked. Thus the antibody binds to an epitope that is lacking on most A antigens, but present on Aw24, A25, A32 and all B and C locus antigens. Comparison of the published amino acid sequences of HLA-A2, A3, Aw24, A28, Cw3, B7, and B40 suggests some possible sites for this epitope. 相似文献
9.
Patient HLA-B27 typing is widely performed as an aid to the diagnosis of several diseases, particularly ankylosing spondylitis. Typing by flow cytometry, using monoclonal antibodies, has been shown to be a potentially useful alternative to classical serology on account of its speed, simplicity and economy. However, we required a flow cytometry typing procedure that would accurately differentiate HLA-B27 (Bw4) from B2708 (Bw6) and not be confounded by other HLA-B7/B27 cross-reactive group antigens. Accordingly, we evaluated the simultaneous use of two monoclonal antibody preparations, ABC-m3-FITC (anti-B27 + weak B7)/BB7.1-PE (anti-B7) and FD705-FITC (anti-B27), by testing a highly selected panel of 62 reference lymphocytes containing examples of all HLA-B7/B27 cross-reactive group antigens, including: HLA-B42, B47, B48, B73, B703, B2702, B2705 and B2708. In addition, 268 whole blood samples from routine patient requests for B27-associated disease typing were tested in parallel with HLA-B typing using the standard complement-dependent microlymphocytoxicity test. The detailed specificity of the three monoclonal antibodies was established and the products of HLA-B*2702, B*2705 and B*2708 were found to be readily differentiated from each other and all other HLA-B7/B27 cross-reactive HLA-B antigens. 相似文献
10.
M. H. Breuning C. J. Lucas B. S. Breur M. Y. Engelsma G. G. de Lange A. J. Dekker W. E. Biddison P. Ivanyi 《Human immunology》1982,5(4):259-268
In the present study cytotoxic T lymphocytes were generated in MLC of lymphocytes from two unrelated HLA-A, B, C-identical, B27-positive, but D/DR-different, individuals. These CTL were shown to detect subtypes of HLA-B27. CTL specific for influenza virus lysed infected target cells matched for HLA-B27 only when they shared the same subtype. This indicates that the two subtypes of HLA-B27 detected by CTL function also as distinct elements in a self-restricted CTL response. Both subtypes were found among patients with ankylosing spondylitis. 相似文献
11.
Kazunaga Agematsu Haruo Nagumo Fen-Chun Yang Takayuki Nakazawa Keitaro Fukushima Susumu Ito Kanji Sugita Tetsuo Mori Tetsuji Kobata Chikao Morimoto Atsushi Komiyama 《European journal of immunology》1997,27(8):2073-2079
B cell immunoglobulin production is regulated by helper T cells through direct interaction and secreted cytokines. In the present study, we functionally analyzed CD27 in cord and peripheral blood B cells. Adult peripheral blood B cells were separated into CD27+ and CD27? cells, which differed in their morphology. Cord blood B cells did not express CD27, and CD27 expression on peripheral blood B cells increased with age. Only CD27+ B cells had the ability to produce immunoglobulin, which was increased by contact with a tumor necrosis factor-related transmembrane ligand, CD70. Adult peripheral blood CD27+ B cells can be further subdivided into two discrete subtypes: IgD?CD27+ and IgD+ CD27+ B cells. IgD? CD27+ B cells produce IgG, IgM and IgA, whereas IgD+ CD27+ B cells predominantly produce IgM. The addition of activated CD4+ CD45RO T cells expressing CD70 caused down-regulation of CD27 expression on activated B cells, and this down-modulation was completely blocked by anti-CD70 monoclonal antibody, indicating direct T-B cell contact via CD27/CD70. The triggering via CD27 and CD40 additively increased the immunoglobulin production under Staphylococcus aureus Cowan strain plus interleukin-2 stimulation. Taken together, our findings demonstrate that peripheral blood B cells are separated into subpopulations by CD27 and IgD expression and that CD27+ B cells produce large amounts of immunoglobulin by interaction with the CD70 molecule. 相似文献
12.
Dissection of the D-region of the human major histocompatibility complex by means of induced mutations in a lymphoblastoid cell line 总被引:9,自引:0,他引:9
This paper describes part of a mutagenic dissection of the human D-region. Twenty-six human lymphoblastoid cell mutants that had lost expressions of HLA-DR were created with a two-step procedure: (i) A mutant from which one entire haplotype had been physically deleted by gamma-rays was isolated by means of immunoselection against cells expressing a specific HLA-B antigen. (ii) This heterozygous deletion mutant was irradiated with gamma-rays or treated with ICR 191, a frameshift mutagen, and mutants that no longer expressed the remaining DR1 antigen were selected with a monoclonal antibody directed against a monomorphic DR determinant. Monoclonal antibody GENOX 3.53 was used to show that four of the gamma-ray induced DR-null mutants did not express the cis-linked MB1/MT1 locus. Since MB1/MT1 was still expressed in the other 16 gamm-ray induced and 6 ICR 191-induced DR-null mutants, the separate loss of expression of MB1/MT1 and DR1 is strong evidence that the DR1 and MB1/MT1 alloantigens are under separate genetic control in the cells we used. Since DR-null mutants bound SB2-specific monoclonal antibody ILR1, whether or not they expressed MB1/MT1, the results mean that gamma-rays resolved the genetic determinants for DR1, MB1/MT1, and SB2. Additional complexity of determinants encoded by D-region genes is indicated by the following results. The amount of MB1/MT1 antigen that was detected with ELISA tests for binding of GENOX 3.53 antibody to cells varied inversely with the number of expressed copies of DR or of a locus near DR. This could result from an increased amount of MB1/MT1 antigen or from increased binding accessibility of GENOZ 3.53-reactive antigen in DR-null mutants. Monoclonal antibodies CC 11.23 and CC 6.4 displayed patterns of binding to parental and diverse mutant cells that differed from that of GENOX 3.53, suggesting the existence of at least one additional D-region antigen that is neither SB, DR, nor MB/MT. 相似文献
13.
Although self-restricted T cells are peptide-specific and can distinguish among closely related ligands, they have some flexibility in the recognition of sequence variants of their natural peptide epitopes. Alloreactive cytotoxic T lymphocytes (CTL) can recognize specific peptides bound to the allo-major histocompatibility complex (MHC) molecule, but their plasticity in the recognition of related peptide variants has not been properly defined. The anti-B*2705 alloreactive CTL 27S69 specifically recognizes a natural octamer ligand of HLA-B*2705. In this study, we tested the recognition of a nested set of epitope variants by this CTL clone. Although none of these peptides was recognized equally as the natural epitope, two of the peptide variants were recognized with only slightly decreased efficiency. Peptide sensitization assays showed that CTL recognition of epitope variants correlated directly with conservation of two non-anchor residues that were critical for recognition of the natural epitope, and inversely with peptide length. Molecular modeling of the peptide variants complexed with B*2705 provided a rational explanation for their differential recognition. Location of the two critical peptide residues at the right three-dimensional space favored efficient recognition by CTL 27S69. The negative effect of increasing peptide length on recognition was due to the bigger bulging surface between the two critical residues, which precluded for optimal interaction with the specific T-cell receptors (TCR). Our results demonstrate that an alloreactive CTL has a degree of plasticity in the recognition of peptide epitope variants that is comparable to that of peptide-specific self-restricted CTL, and define the structural features determining crossreaction among related peptides. 相似文献
14.
Robert A. Colbert Monica L. DeLay Erin I. Klenk Gerlinde Layh-Schmitt 《Immunological reviews》2010,233(1):181-202
Summary: Almost four decades of research into the role of human leukocyte antigen-B27 (HLA-B27) in susceptibility to spondyloarthritis has yet to yield a convincing answer. New results from an HLA-B27 transgenic rat model now demonstrate quite convincingly that CD8+ T cells are not required for the inflammatory phenotype. Discoveries that the HLA-B27 heavy chain has a tendency to misfold during the assembly of class I complexes in the endoplasmic reticulum (ER) and to form aberrant disulfide-linked dimers after transport to the cell surface have forced the generation of new ideas about its role in disease pathogenesis. In transgenic rats, HLA-B27 misfolding generates ER stress and leads to activation of the unfolded protein response, which dramatically enhances the production of interleukin-23 (IL-23) in response to pattern recognition receptor agonists. These findings have led to the discovery of striking T-helper 17 cell activation and expansion in this animal model, consistent with results emerging from humans with spondyloarthritis and the discovery of IL23R as an additional susceptibility gene for ankylosing spondylitis. Together, these results suggest a novel link between HLA-B27 and the T-helper 17 axis through the consequences of protein misfolding and open new avenues of investigation as well as identifying new targets for therapeutic intervention in this group of diseases. 相似文献
15.
The T cell receptor (TcR) on CD8+ T lymphocytes recognizes a complex which consists of a major histocompatibility complex (MHC) heavy chain, β2-microglobulin (β2M), and peptide on the surface of antigen-presenting cells. Mutational analyses have suggested that the TcR recognizes both the αl and α2 domains of the heavy chain as well as the peptide. In light of this, it is of interest to know to what extent the heavy chain domains take on distinct conformations when bound to individual peptides. It has recently been shown that antibodies which recognize the Kb MHC complex are sensitive to which peptides are bound in the groove. We have extended this analysis to include eight Kb-specific antibodies, seven of which are peptide sensitive. These antibodies, all of which are allo-antibodies, recognize Kb-bearing cells which, it is now appreciated, have a highly heterogeneous mix of self peptides presented in their grooves. We show that these self peptides also can affect antibody binding. It has been suggested that peptides alter the conformation of the αl and α2 domains of the heavy chain and that this in turn affects the recognition of Kb by antibody. An alternative hypothesis is that solvent-exposed peptide side chains may prevent the antibody from binding the complex. Using a panel of 128 single-amino acid variants of a Kb-binding antigenic peptide from ovalbumin we show that for most Kb-specific antibodies, the second idea is more likely. Those variants which prevent antibody binding are at solvent exposed positions, and in general, the bulkier the side chain, the greater the inhibition of antibody binding. However, in the case of two antibodies, 100.30 and 34.4.20, the peptide residues which affect antibody recognition are buried, suggesting that these antibodies see an alternate conformation of the peptide/MHC complex. 相似文献
16.
A cytotoxic murine monoclonal antibody recognizing a specific HLA alloantigen was produced from the spleen cells of a BALB/c immunized with partially purified class I glycoproteins from an HLA-A1,B8 homozygous b-lymphoblastoid cell line. The antibody, designated P8.1, was tested against cells from 521 unrelated donors. It reacted with each of the 83 donors known to be HLA-B8 positive and with no HLA-B8 negative donors (sensitivity, 100%; specificity, 100%). Immunoprecipitation with antibody P8.1 and polyacrylamide gel electrophoresis confirmed that the antigen recognized was a class I structure. Although most murine monoclonal anti-HLA antibodies previously described have recognized “public” or supertypic specificities, the identification of a monoclonal antibody specific for a “private” HLA alloantigen indicates first that the BALB/c mouse has the appropriate immune response repertoire for recognizing certain HLA allospecificities and second that HLA-B8 can be defined by a single unique epitope. 相似文献
17.
Joseph A. Trapani Hilary A. Vaughan Rosemary L. Sparrow Brian D. Tait Ian F.C. McKenzie 《Human immunology》1983,7(4):205-216
The production and characterization of a new anti-HLA-B27 monoclonal antibody HLA-ABC-m3 is described. This cytotoxic IgG2a antibody binds protein A and is able to precipitate cell surface molecules of 43,000 and 12,000 daltons corresponding to the HLA heavy chain and β2-microglobulin. Population testing revealed that the HLA-ABC-m3 antibody reacted with the peripheral blood lymphocytes of 47/47 individuals conventionally typed as HLA-B27+ and with 5/105 HLA-B27− individuals. These five extra reactions were with individuals expressing the cross-reactive HLA-B7 alloantigen, although the affinity of the monoclonal antibody for B27 heterozygous individuals (approx 109 M−1) was tenfold greater than with B7 individuals (approx 108 M−1). In addition, HLA-ABC-m3 reactivity segregated with HLA-B27 in two families. This monoclonal antibody should be of value in the investigation of the role of HLA-B27 in disease. 相似文献
18.
A novel T‐cell receptor mimic defines dendritic cells that present an immunodominant West Nile virus epitope in mice
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Sojung Kim Amelia K. Pinto Nancy B. Myers Oriana Hawkins Krysten Doll Saghar Kaabinejadian Jason Netland Michael J. Bevan Jon A. Weidanz William H. Hildebrand Michael S. Diamond Ted H. Hansen 《European journal of immunology》2014,44(7):1936-1946
We used a newly generated T‐cell receptor mimic monoclonal antibody (TCRm MAb) that recognizes a known nonself immunodominant peptide epitope from West Nile virus (WNV) NS4B protein to investigate epitope presentation after virus infection in C57BL/6 mice. Previous studies suggested that peptides of different length, either SSVWNATTAI (10‐mer) or SSVWNATTA (9‐mer) in complex with class I MHC antigen H‐2Db, were immunodominant after WNV infection. Our data establish that both peptides are presented on the cell surface after WNV infection and that CD8+ T cells can detect 10‐ and 9‐mer length variants similarly. This result varies from the idea that a given T‐cell receptor (TCR) prefers a single peptide length bound to its cognate class I MHC. In separate WNV infection studies with the TCRm MAb, we show that in vivo the 10‐mer was presented on the surface of uninfected and infected CD8α+CD11c+ dendritic cells, which suggests the use of direct and cross‐presentation pathways. In contrast, CD11b+CD11c? cells bound the TCRm MAb only when they were infected. Our study demonstrates that TCR recognition of peptides is not limited to certain peptide lengths and that TCRm MAbs can be used to dissect the cell‐type specific mechanisms of antigen presentation in vivo. 相似文献
19.
ObjectivesHuman leukocyte antigen (HLA)-B27 (B27) is the strongest genetic factor associated with development of Ankylosing Spondylitis and other spondyloarthropathies (SpA), yet the role it plays in disease pathogenesis remains unclear. We investigated the expression of potentially pathogenic non-conventional heavy chain forms (NC) of B27 in synovial and intestinal tissues obtained from SpA patients. We also determined the presence of NC-B27 in joints, lymphoid and gastrointestinal tissue from B27 transgenic (TG1) rats with M.tuberculosis-induced SpA.MethodsExpression of NC-B27 in human SpA joints and gut and in (21-3 × 283-2)F1 HLA-B27/Huβ2m rat tissue was determined by immunohistochemistry, flow cytometry and confocal microscopy analysis using HC10 and HD6 antibodies.ResultsBoth HC10- and HD6-reactive HLA molecules were present in synovial tissue from SpA patients. Both NC-B27 and KIR3DL2, a ligand for NC-B27, were expressed in inflamed terminal ileal tissues in patients with early SpA. Infiltrating cells in inflamed joint tissues isolated from B27 TG1 rats expressed high levels of NC-B27. NC-B27 were also expressed in joint-resident cells from ankle and tail joints of B27 TG1 rats prior to clinical arthritis. The expression of NC-B27 on B27 TG1 rat CD11b/c+, CD8α+, cells from spleens and LNs increased with animal age and disease progression.ConclusionsNon-conventional HLA class 1 molecules are expressed on resident and infiltrating cells in both synovial and GI tissues in human SpA. NC-B27 expression in joints and lymphoid tissues from B27 TG1 rats prior to the onset of arthritis is consistent with the hypothesis that they play a pathogenic role in SpA. 相似文献
20.
Molecular analysis of the variant alloantigen HLA-B27d (HLA-B*2703) identifies a unique single amino acid substitution 总被引:4,自引:0,他引:4
HLA-B27 is a human major histocompatibility complex class I product defined by its antigenic specificity with conventional alloantisera. Detailed studies using monoclonal antibodies, cytotoxic T lymphocytes (CTL), and isoelectric focusing (IEF) gel electrophoresis demonstrated the heterogeneity in the B27 antigen. We have previously identified a unique variant molecule of B27 designated locally as B27d which is distinguished from other B27 variants by isoelectric point, serologic reactivity, and by a cloned CTL recognition. A gene encoding the B27d variant has been cloned and a complete nucleotide sequence has been determined. Compared to the sequence of the prototype B27a, the B27d has a single base substitution at codon 59 (B27a:TAT--B27d: CAT) in exon 2 responsible for Tyr to His substitution. A His residue at this position in the alpha 1 domain is unique among the known class I sequences and this single amino acid change is apparently sufficient to alter the epitope(s) recognized by antibody and cytotoxic T cell receptor. Previous primary structural analysis of the other five B27 variants has revealed differences of two to four amino acids. The combined structural data on the B27 variants indicate that (1) HLA-B27 represents a family of closely related B locus alleles that share the B27 allospecificity and differ by a limited number (one to four) of amino acid substitutions and (2) point mutation as well as gene conversion might be the mechanism responsible for the allelic variation of B27 antigen family. 相似文献