Functional analysis of the antigen binding region of an MHC class II molecule

Rosloniec, Edward F.; Beard, K. Scott; Freed, John H.

doi:10.1016/0161-5890(93)90117-t

Cited by 6 publications

(3 citation statements)

References 45 publications

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“…A number of groups have analyzed the ability of I-A'' molecules altered by site-directed mutagenesis to bind and present peptide {Griffith et al 1987, Rosloniec et al 1989, Brett et al 1989, Peccoud et al 1990, Warren et al 1990, Wei et al 1991a,b Lee el al. 1991, Graham et al 1992, Rosloniec et al 1993, Bangia et al 1994, Tate et al 1995, Nelson et al 1996. The ability of such class II mutants to bind peptide has usually been inferred by comparing their ability to present peptides to panels of T cells.…”

Section: Mutations Of the I-a'' Alpha Chain Alter Peptide Binding Andmentioning

confidence: 99%

“…Substitution of I-A^ p-chain residues 38 and 61 have very little effect on the binding of a peptide from myelin ba.sic protein (Tate et al 1995). Substitution of I-A'' p-chain positions 65-67 from k-allelic residues to d-allelic residues had no effect on HEL 46-61 binding, while simultaneous replacement of k-allelic residues with d-alle!ic residues on the a-chain at positions 69, 70, 75, and 76 caused between a 3-and 4-fold drop in HEL 46-61 binding (Rosloniec et al 1993). In addition to these data, which were obtained using mutant class II molecules, it has also been shown that the HEL 46-61 peptide can bind to AaVAp*" but not to Aa''/Ap'' heterodimers.…”

Section: Mutations Of the I-a'' Alpha Chain Alter Peptide Binding Andmentioning

confidence: 99%

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Appreciating the Complexity of MHC Class II Peptide Binding: Lysozyme Peptide and I‐A^k

Nelson

Viner

Unanue

1996

Immunological Reviews

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Section: Mutations Of the I-a'' Alpha Chain Alter Peptide Binding Andmentioning

confidence: 99%

Section: Mutations Of the I-a'' Alpha Chain Alter Peptide Binding Andmentioning

confidence: 99%

Appreciating the Complexity of MHC Class II Peptide Binding: Lysozyme Peptide and I‐A^k

Nelson

Viner

Unanue

1996

Immunological Reviews

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“…In many previous studies of the structure-function relationships of MHC class II molecules, mutagenesis has been used to produce individual or multiple interallelic substitutions between two closely related alleles that differ by a few residues (9)(10)(11). For example, the contributions of individual I-El3 residues to T cell responses were investigated by making mutations in El3 k, Eli b, and E/~ s at positions 29, 72, 75, and 79, which correspond to DRB positions 28, 71, 74, and 78 (1,9).…”

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confidence: 99%

Pocket 4 of the HLA-DR(α,β 1*0401) molecule is a major determinant of T cells recognition of peptide.

Fu¹,

Bono²,

Woulfe³

et al. 1995

The Journal of Experimental Medicine

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SummaryTo investigate the functional roles of individual HLA-DR residues in T cell recognition, transfectants expressing wild-type or mutant DR(o~, B1"0401) molecules with single amino acid substitutions at 14 polymorphic positions of the DI~1"0401 chain or 19 positions of the DRo~ chain were used as antigen-presenting cells for five T cell clones specific for the influenza hemagglutinin peptide, HA307-19. Of the six polymorphic positions in the DRB floor that were examined, mutations at only two positions eliminated T cell recognition: positions 13 (four clones) and 28 (one clone). In contrast, individual mutations at DRB positions 70, 71, 78, and 86 on the oe helix eliminated recognition by each of the dones, and mutations at positions 74 and 67 eliminated recognition by four and two clones, respectively. Most of the DRol mutations had minimal or no effect on most of the clones, although one clone was very sensitive to changes in the DRo~ chain, with loss of recognition in response to 10 mutants. Mutants that abrogated recognition by all of the clones were assessed for peptide binding, and only the B86 mutation drastically decreased peptide binding. Single amino acid substitutions at polymorphic positions in the central part of the DRB c~ helix disrupted T cell recognition much more frequently than substitutions in the floor, suggesting that DRB residues on the ol helix make relatively greater contributions than those in the floor to the ability of the DR(oe,~l*0401) molecule to present HA307-19. The data indicate that DRq8 residues 13, 70, 71, 74, and 78, which are located in pocket 4 of the peptide binding site in the crystal structure of the DR1 molecule, exert a major and disproportionate influence on the outcome of T cell recognition, compared with other polymorphic residues.T he MHC molecules on the cell surface have evolved the remarkable capacity to bind and present to T lymphocytes an extremely large number of structurally diverse peptides. Recognition of the appropriate peptide-class II complexes by the antigen-specific TCR leads to CD4 + T cell proliferation and a cascade of cellular immune responses. HLA class II molecules are highly polymorphic, and this structural polymorphism determines the distinct peptide-binding and antigen presentation characteristics of each molecule. However, the functional roles of individual residues in HLA class II molecules in peptide binding and T cell recognition have not been dearly defined. Elucidation of the ways in which class II residues interact with peptides and TCR may have important implications for understanding the function of the This study was presented in part as an abstract at the 19th annual meeting of the American Society for Histocompatibility and Immunogenetics, Phoenix, Arizona, 2-7 October, 1993. immune system, as well as for the treatment ofimmunologically mediated diseases.Considerable progress has been made in the understanding of the structure of HLA class II molecules and the nature of class II-peptide interactions in recent years. Based ...

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Quantitative analysis of peptide–MHC class II interaction

Fleckenstein

Wiesmüller

1999

Seminars in Immunology

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Functional analysis of the antigen binding region of an MHC class II molecule

Cited by 6 publications

References 45 publications

Appreciating the Complexity of MHC Class II Peptide Binding: Lysozyme Peptide and I‐A^k

Appreciating the Complexity of MHC Class II Peptide Binding: Lysozyme Peptide and I‐A^k

Pocket 4 of the HLA-DR(α,β 1*0401) molecule is a major determinant of T cells recognition of peptide.

Quantitative analysis of peptide–MHC class II interaction

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Functional analysis of the antigen binding region of an MHC class II molecule

Cited by 6 publications

References 45 publications

Appreciating the Complexity of MHC Class II Peptide Binding: Lysozyme Peptide and I‐Ak

Appreciating the Complexity of MHC Class II Peptide Binding: Lysozyme Peptide and I‐Ak

Pocket 4 of the HLA-DR(α,β 1*0401) molecule is a major determinant of T cells recognition of peptide.

Quantitative analysis of peptide–MHC class II interaction

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Product

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Appreciating the Complexity of MHC Class II Peptide Binding: Lysozyme Peptide and I‐A^k

Appreciating the Complexity of MHC Class II Peptide Binding: Lysozyme Peptide and I‐A^k