摘要:

Abstract:Amino acid sequences and structural data on HLA class I molecules are now available, making possible a comparison of the serological and structural definitions of allelic series.1) A hierarchy of differences between molecules is observed. Certain molecules show a low level of differences (1.2% of amino acids) and represent variants of original molecules. Other molecules are recombinants derived from two parent molecules (2.5% difference). Original molecules from an allelic series have a higher level of difference (7.6.%). Maximum differences (13.5%) are observed between products from different loci. Serologically related specificities (cross‐reacting groups) show a relatively low level of difference (6.4%).2) In most specificities an exclusive residue can be considered as responsible for the formation of a serologically recognized determinant. Certain specificities do not have an exclusive residue; they can then be characterized either by a unique determinant made by the association of several non‐exclusive residues, or by an unique association of several non‐exclusive (shared) determinants. There is a significant correlation between the absence of an exclusive residue and the absence of monoclonal antibodies recognizing certain specificities. This suggests two kinds of definition of serological specificities, either by a single exclusive determinant (monotopic recognition) or by several shared determinants (polytopic recognition). Private and public specificities are recognized at the structural level. T‐cell receptor (TCR) recognizes either a xenogeneic peptide in the context of self HLA molecules (restricted CTL [Cytotoxic T Lymphocyte]), or allogeneic HLA molecules. Determinants recognized by CTL (restricted or allogeneic) on HLA molecules have been identified. It is not possible to ascertain whether determinants recognized by antibodies and TCRs are identical, but they are probably very similar.3) HLA class I molecule is made of 75% conserved residues (mostly in the α3and β2‐m domains) and of 25% variable residues (mostly in the α1+α2domains). Conserved residues maintain the general shape of the molecule, its outward orientation on the cell membrane, its association with T cells CD8 molecule, and the structure of the peptide binding site, a groove at the top of molecule. Variable residues are responsible for the capacity of each molecule to bind and to present a large number of different peptides to the TCR. Each molecule carries several (3–10?) variable sites; certain are localized into the groove and are recognition sites while others, more exposed on the surface of the molecule, are sites recognized by TCRs and antibodies. Both conserved and variable regions are necessary to the function of t

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1990.tb01765.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Abstract:The distribution of HLA‐DP antigens were studied in 41 patients with alopecia areata (AA) and 188 ethnically matched controls. An increase of DR4 and possibly DR5 in 24 of these patients has previously been reported. HLA‐DP typing for DPwl through w6 and the local specificity, CDP HEI, was performed using the primed lymphocyte typing (PLT) technique.The frequencies of DPw4 were 92.9% in AA patients and 71.3% in controls (relative risk, RR = 5.1, p = 0.0019 and p<0.03 when corrected). DPwl was decreased to 4.9% in patients compared to 14.9% in controls, but the difference was not statistically significant. The frequency of DR4 was 48.8% compared to 31.9% in controls (RR = 2.0) whereas the frequency of DR5 did not differ from that in controls.DPw4 was not associated (in linkage disequilibrium) with DR4 or DR5 in patients or controls. Thus, in AA the association with DP and DR are independent of each other. However, individuals with both the DPw4 and DR4 alleles are at increased risk for AA, indicating that synergism between DP and DR gene products may play a role in the genetic susceptibility to

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1990.tb01766.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1990.tb01767.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Abstract:The cytoplasmic domain of the CD45 leukocyte cell surface antigen has recently been shown to possess protein tyrosine phosphatase (PTPase) activity. The existence of a cell membrane‐bound PTPase may represent a mechanism by which an activation signal, initiated by ligand binding to a surface receptor, is down‐regulated following delivery of the signal. Both the interleukin‐2 (IL2) growth factor receptor and the CD3/Ti T‐cell antigen receptor contain a subunit which is phosphorylated on tyrosine by an activated protein tyrosine kinase (PTK) during T‐cell activation. We compared the effect of CD45 ligation on signal transduction mediated by the binding of IL2 or anti‐CD3 to these two receptors. Immunoblotting with anti‐phosphotyrosine antiserum was used to investigate the effect of CD45 ligation on anti‐CD3‐ or IL2‐induced protein tyrosine phosphorylation. When CD3 and CD4S were triggered together, changes in the pattern of tyrosine phosphorylation of specific substrates was observed in comparison to the stimulus triggered through CD3 alone. In contrast, CD45 ligation did not alter the pattern of tyrosine‐phosphorylated proteins in “resting” T‐cell blasts responding to IL2, except for a mobility shift of a 55 kDa protein and increased phosphorylation of a 112 kDa substrate. The proliferative response of T cells to both anti‐CD3 or IL2 was inhibited by ligating CD45. The CD45 molecule down‐regulated CD3‐induced T‐cell activation when the CD45 and CD3 molecules were ligated simultaneously with immobilized antibodies. In contrast, immobilized CD45 mAb alone inhibited IL2‐induced proliferation, and the inhibition was not potentiated by simultaneously using a CD25 mAb which was non‐competitive for IL2‐binding. Furthermore, soluble anti‐CD4S partially inhibited proliferation in response to IL2, indicating that proximal association of CD45 and IL2 receptor molecules was not required for inhibition. We conclude that the PTPase activity of CD45 can uncouple both the antigen‐mediated and 112–mediated pathways of signal transduction in T cells, bu

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1990.tb01768.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Abstract:The major histocompatibility complex (MHC) class II antigens (Ags) are known to carry the major stimulating determinants of the primary mixed lymphocyte reactions (MLR). We investigated the mechanism of generating HLA class I‐directed alloreactive T‐cells in primary MLR. With the use of class II‐deficient EBV‐transformed B‐lymphoblastoid cell lines (B‐LCLs) derived from patients with bare lymphocyte syndrome (BLS), we have demonstrated in the present study that class I disparity alone can trigger primary MLR in the absence of exogenous IL‐2. The CD8+T cells were primary MLR‐responsive cells, and the CD4+T cells seem to play no role in primary MLR when class II alloantigens are not involved in stimulation. Addition of autologous macrophages did not influence the primary MLR response. The primary MLR was completely blocked by anti‐class I or anti‐CD8 antibodies but not by anti‐class II or anti‐CD4 antibodies. The MLC‐generated CD8+T cells exhibited cytolytic activity as well as proliferative responses. The proliferative response of the CD8+T cells was specifically directed against class I antigens, demonstrated by proliferatlire assays; and the helper‐independent CD8+. T cells were generated only when the activation of CD4+T cells did not occur. This observation suggests that functional recruitment of T‐cell receptor (TCR) repertoire is under active regulation, and the suppression of CD8+T‐cell helper recruitment appears to be dictated by the CD4+T‐cell subset. Further analysis of the primed T‐cell specificities showed that alloreactivity of the CD8+T cells was mostly accounted for by the HLA‐B Ags. The higher alloreactivity against the HLA‐B Ags may probably be due to the high frequency of HLA‐B‐directed T‐cell clones, and the high frequency is probably due to their higher sequence variabi

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1990.tb01769.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Abstract:We investigated theTaqI digested DNA restriction fragment length polymorphism (RFLP) of the Major Histocompatibility Complex (MHC) class II genes: HLA‐DRB, ‐DQA, and the class III genes: C4 and 21‐hydroxylase(CYP21) in 56 caucasoid patients with systemic lupus erythematosus (SLE) and 62 control subjects in order to define the molecular variation of these genes and their association with SLE. The results showed that the gene frequencies of both HLA‐DR2 and ‐DR3 were significantly increased in the SLE population compared to normal subjects (DR2: 21.4% vs 10.7%; χ2= 4.5. DR3: 29.6% vs 13.3%; χ2= 8.3). A high frequency of C4A and CYP21A gene deletions was also found in SLE patients (SLE 52%, normals 24%). All of 22 SLE patients, and 12 of 15 normal subjects who had C4A and CYP21A gene deletions had a 10.0kbTaq1 DRB RFLP attributable to the presence of HLA‐DR3. Family studies showed linkage of C4A/CYP21A deletions with HLA‐B8 and ‐DR3, and confirmed the previously demonstrated association of the HLA‐B8, DR3, C4A*Q0, C4*B1, Bf*S, C2*C haplotype with SLE. Deletions affecting the C4A and CYP21A genes were the commonest cause of C4A null alleles in SLE. No strong association between C4 null phenotype or C4 gene deletion, as determined by RFLP, was observed in patient

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1990.tb01770.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1990.tb01771.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY