Intramolecular immunodominance and intermolecular selection of H2d-restricted peptides define the same immunodominant region of the measles virus fusion protein

Bünder, Robert; Mayser, Helmut; Ammon, Susanne; Weinmann, Martin; Brons, Nicolaas H. C.; Schneider, François; Jung, Günther; Wiesmüller, Karl‐Heinz

doi:10.1016/0161-5890(94)00132-k

Cited by 17 publications

(23 citation statements)

References 53 publications

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“…That this is possible in the case of DQ has been shown previously (26) and suggested in modeling studies (66). Furthermore, this type of cross-reactivity is perhaps related to the previously reported phenomenon of epitope/motif clustering, or "hot spots" (79)(80)(81)(82)(83)(84)(85). It has been reported that certain protein regions are targets of T cells restricted by multiple HLA specificities that recognize overlapping, yet distinct, peptides.…”

Section: Discussionmentioning

confidence: 57%

Divergent Motifs but Overlapping Binding Repertoires of Six HLA-DQ Molecules Frequently Expressed in the Worldwide Human Population

Sidney

Steen

Moore

et al. 2010

The Journal of Immunology

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Knowledge of the binding repertoires and specificities of HLA-DQ molecules is somewhat limited and contradictory, partly because of the scarcity of reports addressing some of the most common molecules and possibly because of the diversity of the techniques used. In this paper, we report the development of high-throughput binding assays for the six most common DQ molecules in the general worldwide population. Using comprehensive panels of single substitution analogs of specific ligands, we derived detailed binding motifs for DQA1*0501/DQB1*0301, DQA1*0401/DQB1*0402, and DQA1*0101/DQB1*0501 and more detailed motifs for DQA1*0501/DQB1*0201, DQA1*0301/DQB1*0302, and DQA1*0102/DQB1*0602, previously characterized on the basis of sets of eluted ligands and/or limited sets of substituted peptides. In contrast to what has previously been observed for DR and DP molecules, DQ motifs were generally less clearly defined in terms of chemical specificity and, strikingly, had little overlap with each other. However, testing a panel of peptides spanning a set of Phleum pratense Ags, and panels of known DQ epitopes, revealed a surprisingly significant and substantial overlap in the repertoire of peptides bound by these DQ molecules. Although the mechanism underlying these apparently contradictory findings is not clear, it likely reflects the peculiar mode of interaction between DQ (and not DR or DP) molecules and their peptide ligands. Because the DQ molecules studied are found in >85% of the general human population, these findings have important implications for epitope identification studies and monitoring of DQ-restricted immune responses.

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Section: Discussionmentioning

confidence: 57%

Divergent Motifs but Overlapping Binding Repertoires of Six HLA-DQ Molecules Frequently Expressed in the Worldwide Human Population

Sidney

Steen

Moore

et al. 2010

The Journal of Immunology

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“…It is also possible that instances of epitopes exhibiting intralocus or interlocus cross-reactivity may not always be due to the presence of a single promiscuous core region, but rather may be caused by multiple overlapping core regions, each binding different HLA molecules. This type of cross-reactivity might be related to the previously reported phenomenon of epitope/motif clustering, or "hot spots" (36,(85)(86)(87)(88)(89)(90). It was reported that certain protein regions are targets of T cells restricted by multiple HLA specificities that recognize overlapping, yet distinct, peptides.…”

Section: Discussionmentioning

confidence: 88%

Five HLA-DP Molecules Frequently Expressed in the Worldwide Human Population Share a Common HLA Supertypic Binding Specificity

Sidney

Steen

Moore

et al. 2010

The Journal of Immunology

121

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Compared with DR and DQ, knowledge of the binding repertoires and specificities of HLA-DP alleles is somewhat limited. However, a growing body of literature has indicated the importance of DP-restricted responses in the context of cancer, allergy, and infectious disease. In the current study, we developed high-throughput binding assays for the five most common HLA-DPB1 alleles in the general worldwide population. Using these assays on a comprehensive panel of single-substitution analogs and large peptide libraries, we derived novel detailed binding motifs for DPB1*0101 and DPB1*0501. We also derived more detailed quantitative motifs for DPB1*0201, DPB1*0401, and DPB1*0402, which were previously characterized on the basis of sets of eluted ligands and/or limited sets of substituted peptides. Unexpectedly, all five DP molecules, originally selected only on the basis of their frequency in human populations, were found to share largely overlapping peptide motifs. Testing panels of known DP epitopes and a panel of peptides spanning a set of Phleum pratense Ags revealed that these molecules also share largely overlapping peptide-binding repertoires. This demonstrates that a previously hypothesized DP supertype extends far beyond what was originally envisioned and includes at least three additional very common DP specificities. Taken together, these DP supertype molecules are found in >90% of the human population. Thus, these findings have important implications for epitope-identification studies and monitoring of human class II-restricted immune responses.

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“…Serial two-or fourfold dilutions of each serum were tested by ELISA [9,10] MV-ELISA. Antibodies cross-reacting with the MV were monitored with a commercial ELISA based on MV-infected diploid human cells (Enzygnost; gift from Dr Giesendorf, Behringwerke Marburg, Germany) as described previously [8]. End-point titres correspond to the highest dilution which gave a 1 O.D.…”

Section: Methodsmentioning

confidence: 99%

“…Neutralization assay. Heat-inactivated serum was diluted 1:20 and tested for neutralizing activity on MV-infected Vero cell cultures as described [8].…”

Section: Methodsmentioning

confidence: 99%

“…In a previous study, we have defined H2 d -restricted T-cell epitopes of the measles virus (MV) by peptide-mediated T-cell proliferation, using a set of overlapping 15-mer peptides covering the whole sequence of the fusion (F) protein. The immunodominance between the most important T-cell epitopes was also investigated in this study [8]. Therefore, this system is useful for studying the influence of selected T-cell epitopes on the ability of a large number of peptides to induce antibodies.…”

Section: Introductionmentioning

confidence: 99%

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Hierarchic T‐Cell Help to Non‐Linked B‐Cell Epitopes

et al. 1996

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The induction of antibodies against peptides requires the presence of a T helper cell epitope. In the absence of an added T-cell epitope only 10% of the mice, or less depending on the strain, gave an antibody response to a series of peptides of the measles virus (MV) fusion (F) protein. After coimmunization with a non-covalently coupled T-cell epitope more than 60% of the peptides became immunogenic. Considerable differences became apparent when BALB/c mice were immunized with peptides in the presence of different T-cell epitopes. An immunodominant T-cell epitope of the MV-F protein was more efficient than a subdominant or a cryptic T-cell epitope in providing help to a non-linked B-cell epitope. There is both a ranking order of the amount of help which B-cell epitopes require and a ranking order for the help T-cell epitopes are able to provide. The capability of a T-cell epitope to provide help to a B-cell epitope correlated with its own immunogenicity, i.e. the intensity of the antibody response to the peptide representing the T-cell epitope. The data suggest that for each MHC class II allele there is an optimal T-cell epitope which can provide help to a maximal number of B-cell epitopes and that such a peptide can be identified by its ability to induce antibodies against itself. By using this strategy, the authors were able to induce antibodies which cross-reacted with the MV.

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Intramolecular immunodominance and intermolecular selection of H2d-restricted peptides define the same immunodominant region of the measles virus fusion protein

Cited by 17 publications

References 53 publications

Divergent Motifs but Overlapping Binding Repertoires of Six HLA-DQ Molecules Frequently Expressed in the Worldwide Human Population

Divergent Motifs but Overlapping Binding Repertoires of Six HLA-DQ Molecules Frequently Expressed in the Worldwide Human Population

Five HLA-DP Molecules Frequently Expressed in the Worldwide Human Population Share a Common HLA Supertypic Binding Specificity

Hierarchic T‐Cell Help to Non‐Linked B‐Cell Epitopes

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