Mutagenesis around residue 176 on HLA-B∗0702 characterizes multiple distinct epitopes for anti-HLA antibodies

McCutcheon, Jane A.

doi:10.1016/0198-8859(92)90020-n

Cited by 20 publications

(23 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this scenario, anti-PQR antibodies will react only with X and Y because the PQR-carrying Z lacks the critical contact site necessary for binding with antibody. Recent studies have verified the role of critical contact sites in reactions with HLA antibodies [19] and other reported data are consistent with this notion [87][88][89] Depending on the HLA type of the antibody producer, the polymorphic residues of a critical contact site on the immunizing antigen can be self or non-self. In the latter case, this might lead to antibodies against epitopes defined by combinations of non-self eplets and non-self critical contact sites.…”

Section: Discussionsupporting

confidence: 54%

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: Discussionsupporting

confidence: 54%

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

2006

View full text Add to dashboard Cite

show abstract

“…It should be pointed out that most residues within 15 Å of a given eplet are monomorphic and that the compositions of current Luminex panels do not permit further analysis. More detailed descriptions of structural epitopes seem possible by testing mAbs with alleles with informative point mutations [37,38] or, better yet, by analyzing crystallized HLA antigen-antibody complexes similar to that described by Ziegler's group [39]. Nevertheless, our model of surface residues within a 15-Å radius of a centrally located eplet offers a reasonable estimate of a structural epitope contacted by a specific HLA antibody.…”

Section: Molecular Modeling Of the Topography Of Structural Epitopesmentioning

confidence: 93%

“…For the 5 eplets in this study, we have calculated from the models in Fig. 1 that eplets and their corresponding 15-Å 2 surface areas have an average of 33 residue locations (range [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40]. These numbers are higher than the general 15 to 25 range of contact residues in structural epitopes of experimentally tested protein antigens.…”

Section: Molecular Modeling Of the Topography Of Structural Epitopesmentioning

confidence: 97%

Structural aspects of human leukocyte antigen class I epitopes detected by human monoclonal antibodies

Duquesnoy¹,

Marrari²,

Mulder³

et al. 2012

Human Immunology

View full text Add to dashboard Cite

“…The remainder of the tobacco-treated cells were divided into the following groups: 1) treated, untransfected; 2) treated TAP1 transfected; and 3) treated vector transfected. The transfections were performed as described (23). Twenty-four hours after transfection, an aliquot of untreated and tobacco-treated cells from the three groups was collected for flow cytometry and Western blot.…”

Section: Transfection Of Tobacco-treated Cellsmentioning

confidence: 99%

“…Flow cytometry was performed as described (23). Briefly, cells were stained with CVC7, an anti-clatherin Ab as an isotype control (25), W6/32, against assembled HLA class I (CVC7 and W6/32 were prepared as supernatants from hybridoma cell lines obtained from American Type Culture Collection, Manassas, VA), followed by goat anti-mouse IgG-FITC (Fisher, Houston, TX).…”

Section: Flow Cytometrymentioning

confidence: 99%

Tobacco Reduces Membrane HLA Class I That Is Restored by Transfection with Transporter Associated with Antigen Processing 1 cDNA

Fine

Han

Sun

et al. 2002

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

HLA class I molecules are recognized by CTL that eliminate virally infected and malignantly transformed cells presenting foreign peptide—a process termed immunosurveillance. Many tumors have reduced levels of membrane HLA class I. Tumor cells with mutations that reduce HLA class I avoid immunosurveillance and continue to proliferate. As tobacco use can induce tumors, we examined the effect of tobacco extracts on membrane HLA class I. These studies show that culture of cells in media containing tobacco extracts reduces membrane HLA class I, but not other proteins, on primary keratinocytes and other cell types. Culture in tobacco extracts, but not extracts of other substances, reduces TAP1 protein, but does not reduce expression of HLA class I H chain, L chain, or the housekeeping protein β-actin. The reduction of TAP1 protein occurs within 4 h and is dose-dependent. Culture in tobacco extracts reduces TAP1 protein abundance, but not steady-state mRNA abundance. Tobacco-treated cells show defects in HLA class I biosynthesis similar to those found in TAP1-deficient cell lines. Transfection with TAP1 cDNA restores TAP1 protein abundance, HLA class I biosynthesis, and cell surface expression. Combined, these data show that culture in tobacco extracts reduces TAP1 protein abundance and membrane HLA class I levels. Reduction in membrane HLA class I could permit subsequent malignant transformation of cells to be undetected by the immune system.

show abstract

Mutagenesis around residue 176 on HLA-B∗0702 characterizes multiple distinct epitopes for anti-HLA antibodies

Cited by 20 publications

References 34 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

Structural aspects of human leukocyte antigen class I epitopes detected by human monoclonal antibodies

Tobacco Reduces Membrane HLA Class I That Is Restored by Transfection with Transporter Associated with Antigen Processing 1 cDNA

Contact Info

Product

Resources

About