Contribution of T-cell receptor-contacting and peptide-binding residues of the class II molecule HLA-DR4 Dw10 to serologic and antigen-specific T-cell recognition

Barber, Linda D.; Bal, Vineeta; Lamb, Jonathan R.; O’Hehir, Robyn E; Yendle, Janet; Hancock, R.J.T.; Lechler, Robert I.

doi:10.1016/0198-8859(91)90107-k

Cited by 29 publications

(10 citation statements)

References 30 publications

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“…In order to map T-cell determinants on DR molecules, several laboratories have used antigen-specific or alloreactive T-cell clones to determine the relative importance of individual polymorphic amino-acids in T-cell recognition [4,5,[23][24][25][26]. By this approach various patterns of cross-reactivity have been described, leading to the concept of shared epitope hypothesis which postulates that specific motifs rather than the entire DR molecule may dictate T-cell specificity [27].…”

Section: Discussionmentioning

confidence: 99%

“…Either none or less functionally important motifs are shared by DRB1*1101 and non-cross-reacting DR molecules (not shown). The 85-86, 67-71 and 57 motifs have been shown to play critical roles in peptide binding or T-cell recognition [5,[23][24][25][26][28][29][30]. That residue 86 must be shared to observe a crossreactivity is expected because this amino acid lines the major pocket of the binding site that interacts with HA residue Y-309 [9].…”

Section: Discussionmentioning

confidence: 99%

“…The 67-71 motif has been shown to be located in a shallower pocket in DR0101 that accommodates HA residue 315. 71, in particular, has been shown to be critical in T-cell recognition and in peptide binding specificity [5,[23][24][25][26]30]. The third shared motif between DRB1*1601, 1101 and 0801 that can be identified, namely 28-31, comprises residue 28 that lines the same pocket as the 67-71 motif.…”

Section: Discussionmentioning

confidence: 99%

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Sharing of Four DR‐β Sequence Motifs Between HLA‐DRB11601 and DRB11101 Correlates with Frequent Degenerate T‐Cell Recognition of HA306–320 Peptide Complexed to these Two Molecules

Zeliszewski¹,

Dorval²,

Golvano³

et al. 1996

Scand J Immunol

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This paper shows that the seven HA306-320 specific T-cell clones isolated from one individual recognize the peptide complexed to both autologous HLA-DRB1*1101 and allogeneic HLA-DRB1*1601 (or DRB5*0201) molecules. For each T-cell clone, a single T-cell receptor (TCR) is involved in the recognition of these two different peptide-DR complexes as evidenced by cold target competition experiments. Yet, the seven T-cell clones express several different TCRs as judged by V beta-J beta usage and fine specificities. Furthermore, one representative clone has the same fine specificity for HA306-320 analogues mutated at epitopic residues irrespective of the use of DR1101 or DR1601 APC. These results suggest that structural differences between DRB1*1101 and DRB1*1601 (or DRB5*0201) do not dramatically influence the orientation of HA306-320 in the grooves such that most residues interacting with TCRs are conserved. In another individual, the same pattern of restriction, i.e. DR1101 + DR1601, was found for several HA306-320 specific clones. Two additional patterns, DR1101 + DR0801 and DR1101 + DR0801 + DR1601, were identified. By comparing DR sequences the authors found that DRB1*1101 and DRB1*1601 share four important motifs, i.e. beta 85-86, beta 67-71, beta 57 and beta 28-31 supposed to line three distinct HLA-DR pockets. Three of these motifs are also shared with DRB1*0801. All the results further support that the motif similarities allow the peptide to adopt very similar orientations in the cross-reacting DR molecules.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Sharing of Four DR‐β Sequence Motifs Between HLA‐DRB11601 and DRB11101 Correlates with Frequent Degenerate T‐Cell Recognition of HA306–320 Peptide Complexed to these Two Molecules

Zeliszewski¹,

Dorval²,

Golvano³

et al. 1996

Scand J Immunol

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“…7 It is known that residues Gln70 or Asp70 definitely influence two polymorphic DR B-cell epitopes discriminated by the mouse mAb Tal 16.1 7,15 and the human mAb NI. 16 Therefore, we propose that in our system, residue 70 is exposed on the surface of the DR molecule independently of the bound peptide and directly affects the interaction between the TCR and the DR molecule.…”

Section: Discussionmentioning

confidence: 99%

Role of polymorphic residues of human leucocyte antigen‐DR molecules on the binding of human immunodeficiency virus peptides

et al. 1996

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SUMMARYA study was made of the binding properties of 96 human immunodeficiency virus peptides to human leucocyte antigen (HLA)-DR1 and HLA-DR103 molecules, which differ by three amino acids at positions 67, 70 and 71 in the b chains. The affinity of the peptides was characterized by their inhibitory concentrations in competitive binding assays which displace half of the labelled influenza haemagglutinin peptide ). Among the high-affinity peptides (IC 50 4 1 m M), seven bound to DR1, three to DR103 and five equally well to both alleles (promiscuous peptides). Thirty-two other peptides showed medium or low affinity for DR molecules. The role of polymorphic residues was analysed using six mutated DR molecules, intermediates between DR1 and DR103 and differing by one or two substitutions at positions 67, 70 or 71. We reached the same conclusions when using DR1-specific or DR103-specific peptides: modification of residue 70 had no effect on peptide affinity, but single substitution at positions 67 or 71 decreased the allele specificity of the peptides while double substitution at 67 and 71 completely reversed the peptide specificity. In functional assays, DR-binding peptides are able to outcompete specific T-cell proliferation. Furthermore, modification at position 67 or 70 significantly affects the T-cell response and mutation at position 71 abolishes completely the T-cell proliferation. Thus, the polymorphic positions 67 and 71 contributed to the peptide binding with direct effects on T-cell receptor (TCR) recognition while position 70 seems to be mostly engaged in TCR interactions. Furthermore, our results suggest that polymorphic residues may select allele-specific peptides and also influence the conformation of promiscuous peptides.

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“…It seems, therefore, that DRa appears to have evaded the pressure within the MHC to become polymorphic. allele with which it is paired [45]. and Ea.…”

Section: Introductionmentioning

confidence: 99%

Studies on the Interaction of T-Cells with Major Histocompatibility Complex Class II Antigens

Warrens

1997

Clinical Science

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1. Major histocompatibility complex class II antigens have the central role in the immune response of 'presenting' antigenic peptide to CD4+ T-cells. This interaction with a T-cell's receptor may result in activation, but, if recognition occurs without collateral molecular interactions which cause 'co-stimulation', these T-cells will be tolerized. 2. In the light of current interest in muscle cell transplantation, a transformed myoblast, TE671, phenotypically comparable to untransformed cells, transfected to express class II, was studied as a stable model of antigen presentation by muscle cells. These cells failed to activate T-cells but induced tolerance. 3. The DR alpha chain is unusual being the only non-polymorphic classical class II polypeptide, raising the question of its functional contribution. To this end, several single polypeptide constructs were generated with contributions from different class II alpha-chains. On this basis, it was established that DR alpha makes significant contributions to peptide binding and that its alpha 2 domain is also important in T-cell recognition, possibly through CD4 binding. 4. One implication of the lack of polymorphism of DR alpha may be that it has a wider range of pairing partners, possibly including beta chains of different isotypes. To address this, it is planned to use transfectants expressing only a mixed isotype pair to generate T-cell clones in vitro. These reagents would be useful tools to detect whether such mixed pairs exist physiologically. In this paper, the development of a system is described which will allow this question to be addressed.

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Contribution of T-cell receptor-contacting and peptide-binding residues of the class II molecule HLA-DR4 Dw10 to serologic and antigen-specific T-cell recognition

Cited by 29 publications

References 30 publications

Sharing of Four DR‐β Sequence Motifs Between HLA‐DRB11601 and DRB11101 Correlates with Frequent Degenerate T‐Cell Recognition of HA306–320 Peptide Complexed to these Two Molecules

Sharing of Four DR‐β Sequence Motifs Between HLA‐DRB11601 and DRB11101 Correlates with Frequent Degenerate T‐Cell Recognition of HA306–320 Peptide Complexed to these Two Molecules

Role of polymorphic residues of human leucocyte antigen‐DR molecules on the binding of human immunodeficiency virus peptides

Studies on the Interaction of T-Cells with Major Histocompatibility Complex Class II Antigens

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Contribution of T-cell receptor-contacting and peptide-binding residues of the class II molecule HLA-DR4 Dw10 to serologic and antigen-specific T-cell recognition

Cited by 29 publications

References 30 publications

Sharing of Four DR‐β Sequence Motifs Between HLA‐DRB1*1601 and DRB1*1101 Correlates with Frequent Degenerate T‐Cell Recognition of HA306–320 Peptide Complexed to these Two Molecules

Sharing of Four DR‐β Sequence Motifs Between HLA‐DRB1*1601 and DRB1*1101 Correlates with Frequent Degenerate T‐Cell Recognition of HA306–320 Peptide Complexed to these Two Molecules

Role of polymorphic residues of human leucocyte antigen‐DR molecules on the binding of human immunodeficiency virus peptides

Studies on the Interaction of T-Cells with Major Histocompatibility Complex Class II Antigens

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Product

Resources

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Sharing of Four DR‐β Sequence Motifs Between HLA‐DRB11601 and DRB11101 Correlates with Frequent Degenerate T‐Cell Recognition of HA306–320 Peptide Complexed to these Two Molecules

Sharing of Four DR‐β Sequence Motifs Between HLA‐DRB11601 and DRB11101 Correlates with Frequent Degenerate T‐Cell Recognition of HA306–320 Peptide Complexed to these Two Molecules