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Results for “HLA-DR1 Antigen”

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At least 19 recordsLinked to original sources
PubMed1992

Extensive study of DRB, DQA, and DQB gene polymorphism in 23 DR2-positive, insulin-dependent diabetes mellitus patients.

To gain insight into the HLA subregions involved in protection against insulin-dependent diabetes mellitus (IDDM) we investigated the polymorphism of HLA-DR and -DQ genes in 23 DR2 IDDM patients. Results show the following. (1) Fourteen patients (61%) possess the DRB1, DRB5, and DQB1 alleles found in DRw16/DQw5 healthy people. These data contrast with the 5% of DRw16 normally found in DR2 populations and are in agreement with former observations supporting that the DRw16 haplotype is not protective. (2) Nine DR2 patients, i.e., 39% versus 95% in published DR2 controls, possess the DRB alleles found in DRw15 unaffected people. Among them, six patients have also DQA1 and DQB1 alleles identical to those found in DRw15/DQw6 healthy individuals. These data confirm that the DRw15/DQw6 haplotype is protective but indicate that none of the DR or DQ alleles, alone or in association, confers an absolute protection. (3) Our most striking results concern the very high frequency of recombinant haplotypes among the DRw15 patients: 3 of 9. In these three patients recombinations led to the elimination of both DQB1 and DQA1 alleles usually associated with DRw15. This strongly suggests that the occurrence of IDDM in these DRw15 patients is due to the absence of the usual DQ product and thus reinforces the assumption that DQ rather than DR region is involved in the protection conferred by the DRw15/DQw6 haplotype. Finally, analysis of the non-DRw15 haplotypes in heterozygous patients showed that IDDM can occur in the absence of any DQ alpha beta heterodimer of susceptibility.

DNA Probes, HLA↗
PubMed1992

Molecular characterization of a recombinant HLA-DR1/DR2 haplotype.

Serologic analysis of two families identified an HLA-DR haplotype in which DR1 and DR2 cosegregated. DNA-RFLP analysis of these families with an HLA-DRB probe revealed a pattern of hybridization suggestive of a recombination between DR1 and DR15. Following amplification, cloning, and nucleotide sequencing of HLA-DRB-gene second-exon DNA sequences, three DRB amplification products associated with the novel haplotype were identified: these corresponded to DRB1*0101, DR2 pseudogene, and DRB5*0101. Clones representing the DRB1*1501 and DR1 pseudogenes were not identified: oligonucleotide typing with DRB1*1501-specific probes confirmed the absence of this gene within the DR1/DR2 haplotype. We postulate that the DR1/DR2 haplotype represents a recombinant between those of DR1-Dw1 and DR15-Dw2, and that the crossing-over may have been between the DRB1*0101 gene and the DR2 pseudogene. This is further supported by DNA-RFLP analysis with HLA-DQB and DQA CDNA probes, which revealed conserved linkage genes between the DQB1*0501, DQA1*0101, and DRB1*0101 genes.

Base Sequence↗
PubMed1992

Predominant naturally processed peptides bound to HLA-DR1 are derived from MHC-related molecules and are heterogeneous in size.

Peptides bound to class I molecules are 8-10 amino acids long, and possess a binding motif representative of peptides that bind to a given class I allele. In the only published study of naturally processed peptides bound to class II molecules (mouse I-Ab and I-Eb), these peptides were longer (13-17 amino acids) and had heterogenous carboxy terminals but precise amino-terminal truncations. Here we report the characterization of acid-eluted peptides bound to HLA-DR1 by high-performance liquid chromatography, mass spectrometry and microsequencing analyses. The relative molecular masses of the peptides varied between 1,602 and 2,996 (13-25 residues), the most abundant individual M(r) values being between 1,700 and 1,800, corresponding to an average peptide length of 15 residues. Complete sequence data were obtained for twenty peptides derived from five epitopes, of which all but one were from self proteins. These peptides represented sets nested at both the N- and C-terminal ends. Binding experiments confirmed that all of the isolated peptides had high affinity for the groove of DR1. Alignment of the peptides bound to HLA-DR1 and the sequences of 35 known HLA-DR1-binding peptides revealed a putative motif. Although peptides bound to class II molecules may have some related features (due to the nonpolymorphic HLA-DR alpha-chain), accounting for degenerate binding to different alleles, particular amino acids in the HLA-DR beta-chains presumably define allelic specificity of peptide binding.

Amino Acid Sequence↗
PubMed1992

Structural analysis of human anti-mouse H-2E xenorecognition: T cell receptor bias and impaired CD4 interaction contribute to weak xenoresponses.

T lymphocyte responses to the MHC of an evolutionarily distant species are known to be weak compared with responses against allogeneic MHC products within a species. This fact was used to examine the regions of human MHC class II molecules required for the stimulation of strong primary immune responses against MHC alloantigens. A panel of mouse DAP.3 transfectants expressing the products of wild-type and recombinant DR1/H-2Ek MHC class II genes paired to either DR alpha or H-2E alpha genes was generated, and tested as stimulator cells for purified human T cells. A strong proliferative response to DAP.3 transfectants expressing allogeneic HLA-DR molecules was seen. In contrast, weak or absent responses were recorded against DAP.3 cells expressing H-2E molecules. Substitution of the DR1 beta chain with H-2E beta k led to a dramatic loss of recognition; alpha chain substitution had a less marked effect. Furthermore, replacement of the beta 2 domain of DR1 with H-2E sequence caused 90% inhibition, whereas introduction of the beta 2 domain of DR1 into H-2Ek led to a 10-fold increase in T cell response. These results are most readily explained if the beta 2 domain contributes to the interaction site for the CD4 molecule. Substitution of either half of the beta 1 domain led to a marked loss of response. This was more impressive following substitution of the TCR-contacting alpha-helical region of the domain.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1992

HLA-D region genes and rheumatoid arthritis (RA): importance of DR and DQ genes in conferring susceptibility to RA.

The distribution of HLA-D region antigens was studied in three groups (I, IIa, and IIb) of patients with rheumatoid arthritis (RA): group I comprised 43 patients with mild, non-progressive RA, controlled by non-steroidal anti-inflammatory drugs without progression or erosions; group II comprised 94 patients with severe disease, who had earlier been treated with non-steroidal anti-inflammatory drugs and all had incomplete response requiring treatment with gold (sodium aurothiomalate). Of these, 46 patients (group IIa) responded to gold and the disease was well controlled, and the remaining 48 patients (group IIb) did not respond to gold and developed gold induced toxic reactions, including thrombocytopenia or proteinuria, or both. HLA-D region antigens were defined by serological and molecular (Southern blot analysis and oligonucleotide typing) techniques. The results show that DR4 was significantly increased in all three groups of patients. The prevalence of DR1, or DR1 in DR4 negative patients, and DR3 and DR4 associated DQw7 specificities, however, showed differences in these three groups of patients. The prevalence of DR1 and of DR1 in DR4 negative patients was increased only in patients with mild (group I) RA, but not in patients with severe (groups IIa and IIb) disease. On the other hand, the prevalence of DR4 associated DQw7 was significantly increased in patients with severe disease, but not in patients with mild RA. In addition, DR3 was significantly increased only in patients with severe disease who developed gold induced toxic reactions (group IIb). These data suggest that the HLA-D region genes which cause susceptibility to mild RA may be different from those causing susceptibility to severe RA. The results suggest that both DR and DQ (A, B) genes may be important in conferring susceptibility to RA: DR in mild disease and DQ in severe RA.

Antibodies, Antinuclear↗
PubMed1992

HLA-DR antigen linkage of anti-beta receptor antibodies in idiopathic dilated and ischaemic cardiomyopathy.

OBJECTIVE: Immunological mechanisms have been implicated in the pathogenesis of human dilated cardiomyopathy. The presence of autoantibodies against the beta 1 adrenoceptor in a substantial proportion of patients with dilated cardiomyopathy has been described and an association between the HLA-DR4 phenotype and anti-beta receptor antibodies has been identified. The objective of the present study was to examine whether the presence of such antibodies in ischaemic cardiomyopathy was limited to specific HLA-DR phenotypes. DESIGN: The HLA-DR dependence of anti-beta receptor antibodies detected by a ligand binding inhibition assay in patients with dilated cardiomyopathy (n = 68) was compared with that in patients with ischaemic cardiomyopathy (n = 73). RESULTS: 38% of the patients with dilated cardiomyopathy and 22% of those with ischaemic cardiomyopathy had serum anti-beta receptor antibodies. In dilated cardiomyopathy, the presence of anti-beta receptor antibodies was linked to the HLA-DR4 phenotype (that is, 50% of patients with this phenotype were antibody positive) whereas, in those with ischaemic cardiomyopathy HLA-DR1 was over-represented (that is, 37% of the patients with the HLA-DR1 phenotype were antibody positive compared with 17% of the HLA-DR1 negative patients). In both disease entities, the HLA-DR3 phenotype was virtually absent in the anti-beta receptor antibody group. CONCLUSIONS: These results suggest that the presence of anti-beta receptor antibodies is under immune genetic control that may depend on the nature of the underlying disease process.

Adult↗
PubMed1992

Interaction of the pertussis toxin peptide containing residues 30-42 with DR1 and the T-cell receptors of 12 human T-cell clones.

The interaction of the immunodominant pertussis toxin peptide containing residues 30-42 (p30-42) with soluble DR1 molecules and the T-cell receptor (TCR) of 12 DR1-restricted human T-cell clones has been analyzed. Peptide analogues of p30-42 containing single alanine substitutions were used in DR1-binding and T-cell proliferation assays to identify the major histocompatibility complex and TCR contact residues. Each T-cell clone was found to recognize p30-42 with a different fine specificity. However, a common core comprising amino acids 33-39 was found to be important for stimulation of all T-cell clones. Within this core two residues, Leu33 and Leu36, interact with the DR1 molecule, whereas Asp34, His35, Thr37, and Arg39 are important for TCR recognition in most of the clones. Computer modeling of the structure of p30-42 showed that an alpha-helical conformation is compatible with the experimental data. The analysis of TCR rearrangement revealed that the peptide was recognized by T-cell clones expressing different variable region alpha (V alpha) and variable region beta (V beta) chains, although a preferential use of V alpha 8-V beta 13 and V alpha 11-V beta 18 combinations was found in clones from the same donor. Understanding the details of the interaction of antigenic peptides with the major histocompatibility complex and TCR molecules should provide the theoretical basis to design T-cell epitopes and obtain more immunogenic vaccines.

Amino Acid Sequence↗
PubMed1992

T cell receptor V beta gene usage in HLA-DR1-reactive human T cell populations. The predominance of V beta 8.

The functional specificity and T cell receptor (TCR) V beta gene expression of three class II HLA-DR1-reactive human T cell populations were examined. WP2, a renal allograft-derived, long-term CD4+ T cell line, was specifically cytotoxic for DR1, one of the mismatched antigens present on the allograft. Initial studies of WP2 using six TCR V beta-specific mAb revealed a predominance of T cells expressing a member of the V beta 8 gene family. A smaller, yet significant, number of cells expressed TCR using V beta 5.1. Semiquantitative V beta-specific polymerase chain reaction (PCR) analyses of RNA derived from this T cell line confirmed the presence of V beta 8 and V beta 5.1 messages. The PCR signal for V beta 8 was the strongest, followed by those for V beta 4 and V beta 5. An earlier WP2 culture had a very similar PCR profile, with a dominant signal for V beta 8, although signals for V beta 4 and V beta 5 were considerably lower. Previous PCR analyses of eight other renal allograft-derived, long-term T cell lines, grown under identical in vitro conditions, revealed no other example of predominant usage of V beta 8. We established two replicate long-term, anti-DR1 mixed lymphocyte reactions using PBL from two unrelated normal donors as responder and stimulator. The MLR were given alloantigen every 10 days, and RNA was obtained from the cultured cells immediately prior to each stimulation. PCR analyses of RNA taken at 10-day intervals over a total of 60-70 days indicated that, although the MLR were initially quite heterogeneous with regard to V beta message expression, by the end of the fourth or fifth Ag cycle the predominant PCR signals observed in both MLR were for V beta 8. These results suggest that T cells using V beta 8 gene-encoded segments as part of their TCR may have a selective advantage in responses to DR1.

Blotting, Southern↗
PubMed1992

Identification of a motif for HLA-DR1 binding peptides using M13 display libraries.

Oligonucleotides encoding peptides known to bind to HLA-DR1 molecules have been inserted into the gene III of filamentous M13 phages. DR1 molecules purified from human lymphoblastoid cell lines could specifically bind to these peptide sequences expressed on the phage surface. A M13 phage peptide library was next constructed and screened with DR1 molecules. After four rounds of selection, more than 80% of the phages were able to bind to DR1. Competition experiments with both isolated phages and corresponding synthetic peptides showed that the binding was specific. Sequence analysis of the peptide encoding region of 60 phages binding to DR1 molecules and comparison with phages of the original library revealed two potential anchor positions. The first was an aromatic residue (Tyr, Phe, or Trp) at the NH2 terminus of the peptide sequences, and the second was located three residues downstream and consisted of Met or Leu. In addition, the negatively charged amino acids Asp and Glu were mostly excluded from the DR1 binding sequences, and the small amino acid residues Gly and Ala were enriched at position 6. As for DR1, this approach should enable one to easily determine the binding motifs of other MHC class II alleles and isotypes. Furthermore, it could have interesting applications in the design of major histocompatibility complex-specific antagonists.

Amino Acid Sequence↗
PubMed1992

Functional analysis of DR17(DR3)-restricted mycobacterial T cell epitopes reveals DR17-binding motif and enables the design of allele-specific competitor peptides.

We have previously shown that p3-13 (KTIAY-DEEARR) of the 65-kDa heat shock protein (hsp65) of Mycobacterium tuberculosis and Mycobacterium leprae is selected as an important T cell epitope in HLA-DR17+ individuals, by selectively binding to (a pocket in) DR17 molecules, the major subset of the DR3 specificity. We have now further studied the interaction between p3-13, HLA-DR17 and four different TCR (V beta 5.1, V beta 1, and V beta 4) by using T cell stimulation assays, direct peptide-DR binding assays, and a large panel (n = 240) of single amino acid substitution analogs of p3-13. We find that residues 5(I) and 8(D) of p3-13 are important DR17 binding residues, whereas the residues that interact with the TCR vary slightly for each DR17-restricted clone. By using N- and C-terminal truncated derivatives of p2-20 we defined the minimal peptide length for both HLA-DR17 binding and T cell activation: the minimal peptide that bound to DR17 was seven amino acids long whereas the minimal peptide that activated T cell proliferation was eight amino acids in length. Furthermore, two new DR17-restricted epitopes were identified on hsp70 and hsp18 of M. leprae. Alignment of the critical DR17-binding residues 5(I) and 8(D) of p3-13 with these two novel epitopes and two other DR17-binding peptides revealed the presence of highly conserved amino acids at positions n and n + 3 with I, L, and V at position n and D and E at position n + 3. D and E are particularly likely to interact with the DR17-specific, positively charged pocket that we have defined earlier. Based on these results, a set of single amino acid substituted analogs that failed to activate these T cell clones but still bound specifically to DR17 was defined and tested for their ability to inhibit T cell activation by p3-13 or other DR17-restricted epitopes. Those peptides were able to inhibit the response to p3-13 as well as other DR17-restricted mycobacterial epitopes in an allele-specific manner, and are anticipated to be of potential use for immunotherapeutic and vaccine design strategies.

Amino Acid Sequence↗
PubMed1992

Heterogeneity in the anti-HLA-DR immune response elicited by the antiidiotypic monoclonal antibody F5-444. Analysis at the clonal level.

A total of 630 hybridomas were generated from a BALB/c mouse immunized with the anti-id mAb F5-444, which binds an idiotope within the antigen-combining site of mAb AC1.59. The latter recognizes a determinant shared by HLA-DR1, DRw8, DR9 antigens and subtypes of HLA-DR4 and DR6 that is poorly expressed by HLA-DRw16 and DRw17 antigens. Eight anti-anti-id mAb were shown with serological and immunochemical assays to react with HLA-DR antigens. Detailed analysis of these anti-HLA-DR anti-anti-id mAb showed that they differ from the original anti-HLA-DR mAb AC1.59 and among themselves in either isotype, fine specificity, extent of reactivity with the nominal antigen, differential reactivity with soluble or cell-bound antigen, and/or idiotype profile. These observations emphasize the need to characterize a panel of antigen-binding anti-anti-id mAb in order to evaluate the degree of similarity existing between antigen-binding antibodies induced by an anti-id mAb and the original antigen-binding mAb.

Animals↗
PubMed1992

The human class II MHC protein HLA-DR1 assembles as empty alpha beta heterodimers in the absence of antigenic peptide.

We have produced the human class II histocompatibility protein, HLA-DR1, as a soluble, secreted glycoprotein in insect cells infected with baculoviruses carrying truncated alpha and beta subunit genes. The peptide-binding site is empty, and the empty molecules are fully competent to bind antigenic peptide. We used the empty molecules to measure an intrinsic rate for peptide association, and to investigate the role of peptide in stabilizing the class II structure. Peptide binding kinetics for the empty molecule are only 10-fold faster than for peptide exchange into an occupied site, suggesting that a conformational change may accompany peptide binding. The native alpha beta heterodimer assembles in the absence of antigenic peptide, but peptide binding stabilizes the empty heterodimer against aggregation and against SDS-induced denaturation.

Amino Acid Sequence↗
PubMed1992

Self-peptide released from class II HLA-DR1 exhibits a hydrophobic two-residue contact motif.

Peptide fragments of foreign and self-proteins are of great immunologic importance as their binding to major histocompatibility complex (MHC) class I or II molecules makes an interaction with a corresponding T cell receptor possible. Recently, allele-specific peptide sequence motifs proved to be responsible for MHC binding, no matter whether self- or non-self-antigens were involved. Up to now, all investigated human class II-associated peptides were derived from foreign antigenic proteins. Therefore, we undertook sequence and binding analyses with a 16-mer self-peptide (SP3) that has been eluted from HLA-DR1. Here we demonstrate, by synthetic polyalanine-based 13-mer analogues of SP3, that two bulky hydrophobic anchor residues with relative spacing i, i + 8 are sufficient for high affinity binding. This is consistent with the hydrophobic i, i + 8 binding pattern recently found for DR-restricted T cell epitopes. Nevertheless, highly helical alanine-based design peptides with anchor spacing i, i + 9 exhibit maximal affinity, whereas replacement of alanine by helix destabilizing proline abrogates binding. Thus, a two-residue contact motif is the common minimal requirement of self- and foreign peptides for high affinity anchoring to HLA-DR1. In contrast to class I, the anchor spacing of DR1-associated peptides seems to bear some variability due to conformational diversity.

Amino Acid Sequence↗
PubMed1992

Identification of HLA-DR1 beta chain residues critical for binding staphylococcal enterotoxins A and E.

Superantigens are thought to make external contacts with major histocompatibility complex (MHC) class II molecules and with the V beta portion of a T cell antigen receptor (TCR), thereby stimulating entire families of T cells. The precise mapping of superantigen binding sites on class II molecules may provide valuable information on how TCR and MHC molecules interact. Two bacterial superantigens, staphylococcal enterotoxins A and E (SEA/SEE) bind well to most HLA-DR alleles, but poorly to HLA-DRw53. The sequences responsible for this binding were localized to the putative alpha helix of the DR beta chain by measuring toxin binding to a panel of chimeric class II molecules expressed on transfected cells. Binding of SEA/SEE to the DRw14 (Dw9) molecule suggested that the conserved histidine 81 in the beta chain of most DR molecules was important, whereas the tyrosine 81 in the DRw53 beta chain was detrimental for high-affinity binding. To prove this, reciprocal point mutations were introduced in the DR1 and DRw53 beta chains. Mutation of histidine 81 in the DR1 beta chain to tyrosine reduced SEA/SEE binding, but did not prevent recognition of two DR1-restricted peptides by six of eight antigen-specific T cell lines. Conversely, introduction to histidine at position 81 in the DRw53 beta chain restored normal levels of SEA/SEE binding. These data suggest that a binding site of SEA and SEE lies on the outer face of the beta chain alpha helix, pointing away from the antigen-binding groove.

Amino Acid Sequence↗
PubMedDate not supplied

Chemically unrelated mycobacterial peptides as antigens and competitors in antigen recognition by human T cells.

Understanding resistance to mycobacterial infectious diseases requires identification of antigens and epitopes (antigenic determinants) that stimulate cell-mediated immune responses. In this study, a DR1-restricted T cell epitope (residues 1 through 20) of the 19-kD protein of M. tuberculosis was identified. Peripheral blood mononuclear cells from two HLA-DR1 patients with tuberculosis responded not only to the 19-kD immunoblot fraction of M. tuberculosis but also to the peptide 1-20. A M. tuberculosis-reactive T cell clone isolated from one of the patient (whose mononuclear cells showed a stronger proliferative response to the 19-kD protein) recognized the peptide 1-20, while failed to recognize a negative control peptide (residues 65 through 85 of the 65-kD mycobacterial protein: peptide 65-85) or a negative control antigen (candida). The antigen recognition to peptide 1-20 was shown to be DR1 restricted. This MHC restriction was confirmed using a DR1-restricted mycobacterial T cell epitope as competitor. These results demonstrated that this mycobacterial competitor significantly reduced the antigen recognition of peptide 1-20. The reduction observed was dose-dependent.

Antibodies, Bacterial↗
PubMed1992

Transfection of HLA-DR-expressing DAP.3 cells with a cDNA clone encoding the glycosyl phosphatidylinositol-linked form of lymphocyte function associated antigen-3: biochemical features and functional consequences.

Structural and functional aspects of the accessory molecule lymphocyte function associated antigen (LFA)-3 (CD58) have been examined following the transfection of DAP.3 and P815 cells with a cDNA clone encoding the glycosyl phosphatidylinositol (GPI)-linked form of human LFA-3. Despite earlier observations that DAP.3 cells are deficient in GPI anchoring LFA-3 was expressed efficiently on DAP.3, as well as on P815 cells. Immunoprecipitation of LFA-3 from 35S-labelled cells revealed that the molecule expressed on the DAP.3 cells had a molecular weight intermediate between the transmembrane and GPI-linked forms expressed by human B cells. This suggests that the DAP.3 cells have a default pathway whereby the RNA transcript which encodes the GPI-linked form of the molecule can also encode an integral membrane protein. Functionally, expression of LFA-3 by DAP.3 which had previously been transfected with the genes encoding HLA-DR1 led to a marked augmentation of the proliferative response of five out of eight anti-DR1 human T cell clones. This effect was not reproduced when DR1 and LFA-3 were expressed by separate populations of DAP.3 cells, suggesting that the ligands for CD2 and for the T cell's receptor must be expressed on the same cell membrane. Expression of human LFA-3 also led to a substantial increase in the proliferative response of human peripheral blood T cells to a DR alloantigen. Separation of T cells into CD45RO+ and CD45RO- populations revealed that the augmentation was more marked for the memory than the virgin population. The mechanisms responsible for these differences are discussed.

Animals↗
PubMed1992

Genetic control of nonresponsiveness to hepatitis B virus vaccine by an extended HLA haplotype.

We previously reported evidence for a statistical association between the serologically determined HLA-Bw54, DR4 and DRw53 alleles and the non-immune responsiveness to hepatitis B virus surface antigen (HBsAg) in the Japanese population. To identify the locus and allele within the HLA region associated with the nonresponsiveness to HBsAg, serological HLA typing, DNA typing of HLA-DQ and DP alleles using amplified HLA genes and sequence-specific oligonucleotide probes, and restriction fragment length polymorphism (RFLP) analysis of the fourth component of complement (C4) genes were performed in healthy unrelated Japanese vaccinees who were immunized subcutaneously three times with plasma-derived HBsAg vaccine. In nonresponders to HBsAg, the frequencies of HLA-Bw54 cross-reactive epitope group (CREG); (Bw54, Bw55, Bw56 and other Bw22), C4 RFLP (6.5 kb + 12.0 kb), DR4, DRw53 and DQw4 (DQA1*0301-DQB1*0401) were increased and the frequencies of HLA-DR1, DRw6 and DQw1 were decreased as compared with those in healthy unrelated controls. Further analysis revealed that the coexistence of HLA-Bw54CREG and DR4-DRw53-DQw4 (DQA1*0301-DQB1*0401) was associated with the nonresponder group, whereas, donors positive for exclusively either Bw54 CREG or DR4-DRw53-DQw4 (DQA1*0301-DQB1*0401) were not associated with the nonresponder group. Because there is a strong linkage disequilibrium between HLA-Bw54CREG, C4 RFLP (6.5 kb + 12.0 kb) and HLA-DR4-DRw53-DQw4 (DQA1*0301-DQB1*0401) in the Japanese population, the extended HLA-Bw54CREG-C4 RFLP (6.5 kb + 12.0 kb)-DR4-DR-w53-DQw4 (DQA1*0301-DQB1*0401) haplotype may well control nonimmune responsiveness to HBsAg. This extended HLA haplotype controls nonresponsiveness as a dominant genetic trait because all ten heterozygotes and two of three probable homozygotes of this extended HLA haplotype were nonresponders.

Adult↗
PubMed1992

Regrafts.

1. Retransplant survival rates have been increasing at a much faster rate than those of first transplants. The difference between first and second transplant 1-year survival rates has decreased from 8% in 1988 to 2% in 1991. 2. Second transplant recipients given 1-20 pretransplant transfusions had 3-5% higher graft survival rates than nontransfused patients or those given more than 20 transfusions. Transfusions for first or multirenal transplants had no significant impact on survival and in some cases, nontransfused patients had higher graft survival rates. 3. The duration of previous graft survival remains one of the best indicators of how subsequent grafts will survive. The 1-year regraft survival rate for second transplant recipients was 77% when the first transplant had survived longer than 1 year, 69% when first graft survival was 6 months to 1 year, and 60% when first graft survival was less than 3 months (p < 0.005, each comparison). 4. The HLA-DR1 phenotype was associated with higher graft survival than patients lacking HLA-DR1. The difference was 8% at 1 year for second graft recipients (p < 0.001) and 15% for multiply retransplanted patients (p = NS). 5. Repeating an HLA-A or -B locus antigen mismatch from a previous graft had no apparent effect on regraft survival rates. Repeating an HLA-DR locus antigen mismatch, either alone or in combination with other antigens, resulted in a 5-8% decrease in 1-year regraft survival. Although the difference was not statistically significant at 1 year, survival was significantly lower at 2 and 3 years for recipients with repeated HLA-DR antigen mismatches.

Adolescent↗