Genetic and serological heterogeneity of the supertypic HLA-B locus specificities Bw4 and Bw6

Muller, Claude; Engler-Blum, G.; Gekeler, Volker; Steiert, I.; Weiß, Elisabeth H.; Schmidt, Helmut

doi:10.1007/bf02421207

Cited by 106 publications

(57 citation statements)

References 48 publications

(23 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…For instance, the Bw4-associated B38 and the Bw6-associated B39 splits of B16 share a distinct 158T eplet. These splits have identical sequences except in the 79-83 region that has the Bw4/6 epitopes [90,91]. Immunization with 158T may lead to antibodies recognizing only B38 or B39; such antibodies require also reactivity with the Bw4 or Bw6 sequence.…”

Section: Discussionmentioning

confidence: 99%

A Structurally Based Approach to Determine HLA Compatibility at the Humoral Immune Level

2006

View full text Add to dashboard Cite

HLAMatchmaker is a structurally based matching program. Each HLA antigen is viewed as a string of epitopes represented by short sequences (triplets) involving polymorphic amino acid residues in antibody-accessible positions. HLAMatchmaker determines which triplets are different between donor and recipient and this algorithm is clinically useful in determining HLA mismatch acceptability. Triplets provide however an incomplete description of the HLA epitope repertoire and expanded criteria must be used including longer sequences and polymorphic residues in discontinuous positions. Such criteria should consider the structural basis of antibody-antigen interactions including contact areas and binding energy, the essence of antigenicity.This report describes the development of a structurally defined HLA epitope repertoire based on stereochemical modeling of crystallized complexes of antibodies and different protein antigens. This analysis considered also data in the literature about contributions of amino acid residues to antigenantibody binding energy. The results have led to the concept that HLA antigens like other antigenic proteins have structural epitopes consisting of 15-22 residues that constitute the binding face with alloantibody. Each structural epitope has a functional epitope of about 2-5 residues that dominate the strength and specificity of binding with antibody. The remaining residues of a structural epitope provide supplementary interactions that increase the stability of the antigen-antibody complex. Each functional epitope has one or more non-self residues and the term "eplet" is used to describe polymorphic HLA residues within 3.0-3.5 Ångstroms of a given sequence position on the molecular surface. Many eplets represent short linear sequences identical to those referred to as triplets but others have residues in discontinuous sequence positions that cluster together on the molecular surface. Serologically defined HLA determinants correspond well to eplets. The eplet version of HLAMatchmaker represents therefore a more complete repertoire of structurally defined HLA epitopes and provides a more detailed assessment of HLA compatibility.

show abstract

Section: Discussionmentioning

confidence: 99%

A Structurally Based Approach to Determine HLA Compatibility at the Humoral Immune Level

2006

View full text Add to dashboard Cite

show abstract

“…In accordance with Peh and colleagues (38), a defect to build up the Bw4 supertypic determinant was, however, not detected using mAb T116-5-28. This suggests that in the presence of wild-type hTpn, subtle conformational changes are induced in class I HC ␣ 1 helix around residues 80 -83, which appear to be recognized by some Bw4-specific Abs, but not by others (52,61). Similar observations were made when .220.B8 cells transfected with wild-type or soluble hTpn variants were examined with a panel of Bw6-reactive Abs (P. Tan and F. Momburg, unpublished results).…”

Section: Discussionmentioning

confidence: 99%

Recruitment of MHC Class I Molecules by Tapasin into the Transporter Associated with Antigen Processing-Associated Complex Is Essential for Optimal Peptide Loading

Tan

Kropshofer²,

Mandelboim

et al. 2002

The Journal of Immunology

101

137

View full text Add to dashboard Cite

The ER protein tapasin (Tpn) forms a bridge between MHC class I H chain (HC)/β2-microglobulin and the TAP peptide transporter. The function of this TAP-associated complex was unclear because it was reported that soluble Tpn that has lost TAP interaction would be fully competent in terms of peptide loading and Ag presentation. We found, however, that only wild-type human Tpn (hTpn), but not three soluble hTpn variants, a transmembrane domain point mutant of hTpn (L410→F), wild-type mouse Tpn, nor a mouse-human Tpn hybrid, fully up-regulated peptide-dependent Bw4 epitopes when expressed in Tpn-deficient .220.B*4402 cells. Consistent with suboptimal peptide loading, the t1/2 of class I molecules was considerably reduced in the presence of soluble hTpn, hTpn-L410F, and murine Tpn. Furthermore, eluted peptide spectra and the class I-mediated inhibition of NK clones showed distinct differences to the hTpn transfectant. Only wild-type hTpn efficiently recruited HC and calreticulin (Crt) into complexes with TAP and endoplasmic reticulum p57 (ERp57). The L410F mutant was defective in TAP association, but bound to class I molecules, Crt, and ERp57. Mouse Tpn associated with human TAP and ERp57 on the one hand, and with HC and Crt on the other, but failed to recruit normal amounts of HLA class I molecules into the TAP complex. We conclude that the loading with peptides conferring high stability requires the Tpn-mediated introduction of HC into the TAP complex, whereas the mere interaction with Tpn is not sufficient.

show abstract

“…15,16 In particular, all HLA-B specifi cities are grouped in two antigenic families: HLA-Bw4 and HLA-Bw6. 17 HLA-Bw4 and HLA-Bw6 epitopes consist of a single epitope in each HLA-B molecule and they are different from the epitopes that establish the HLA-B specifi city; therefore each HLA-B molecule expresses only one of the serological epitopes HLA-Bw4 or HLA-Bw6. HLA-Bw4 is one of the inhibitory or activating ligands for KIR 18,19 that control the natural killer (NK) cell cytotoxic activity.…”

Section: Introductionmentioning

confidence: 99%

HLA-Bw4-B57 and Cw18 alleles are associated with plasma viral load modulation in HIV-1 infected individuals in Salvador, Brazil

Silva¹,

Acosta²,

Santos³

et al. 2010

Braz J Infect Dis

View full text Add to dashboard Cite

Host genetic factors play an important role in mediating resistance to HIV-1 infection and may modify the course of infection. HLA-B alleles (Bw4 epitope; B*27 and B*57) as well as killer cell immunoglobulin-like receptors have been associated with slow progression of HIV-1 infection. Objective: To evaluate the association between serological epitopes HLA-Bw4 and HLA-Bw6 and prognostic markers in AIDS. Methods: 147 HIV-infected individuals in Bahia, Northeast Brazil, were genotyped for HLA class I locus. HLA class I genotyping was performed by hybridization with sequence-specifi c oligonucleotide probes following amplifi cation of the corresponding HLA-A, HLA-B and HLA-C genes. Statistical analysis was performed using Fisher´s exact and ANOVA tests for categorical and continuous variables, respectively. Results: We detected a signifi cant association (χ 2 = 4.856; p = 0.018) between the presence of HLA-Bw4 and low levels of viremia. Eighteen out of the 147 HIV-infected individuals presented viremia  1,800 copies/mL and 129 presented viremia > 2,000 copies/mL. Ninety and four percent (17/18) of all individuals with viremia  1,800 copies/ mL carried HLA-Bw4, compared to 67.4% (87/129) of individuals with viremia > 2,000 copies/mL. Additionally, we found a signifi cantly higher frequency of B*57 (OR = 13.94; 95% CI = 4.19-46.38; p < 0.0001) and Cw*18 (OR = 16.15; 95% CI = 3.46-75.43; p ≤ 0.0001) alleles, favoring the group with lower viremia levels, in comparison with those with higher viral load. Conclusion: HLA-Bw4-B*57 and Cw*18 alleles are associated with lower level of viral load in HIV-infected Brazilian patients. These fi ndings may help us in understanding the determinants of HIV evolution in Brazilian patients, as well as in providing important information on immune response correlates of protection for such population.

show abstract

Genetic and serological heterogeneity of the supertypic HLA-B locus specificities Bw4 and Bw6

Cited by 106 publications

References 48 publications

A Structurally Based Approach to Determine HLA Compatibility at the Humoral Immune Level

A Structurally Based Approach to Determine HLA Compatibility at the Humoral Immune Level

Recruitment of MHC Class I Molecules by Tapasin into the Transporter Associated with Antigen Processing-Associated Complex Is Essential for Optimal Peptide Loading

HLA-Bw4-B57 and Cw18 alleles are associated with plasma viral load modulation in HIV-1 infected individuals in Salvador, Brazil

Contact Info

Product

Resources

About

Genetic and serological heterogeneity of the supertypic HLA-B locus specificities Bw4 and Bw6

Cited by 106 publications

References 48 publications

A Structurally Based Approach to Determine HLA Compatibility at the Humoral Immune Level

A Structurally Based Approach to Determine HLA Compatibility at the Humoral Immune Level

Recruitment of MHC Class I Molecules by Tapasin into the Transporter Associated with Antigen Processing-Associated Complex Is Essential for Optimal Peptide Loading

HLA-Bw4-B*57 and Cw*18 alleles are associated with plasma viral load modulation in HIV-1 infected individuals in Salvador, Brazil

Contact Info

Product

Resources

About

HLA-Bw4-B57 and Cw18 alleles are associated with plasma viral load modulation in HIV-1 infected individuals in Salvador, Brazil