Structure of Antibody-Antigen Complexes: Implications for Immune Recognition

Colman, P.M.

doi:10.1016/s0065-2776(08)60364-8

Cited by 207 publications

(100 citation statements)

References 124 publications

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“…In 1960, Niels Jerne coined the term epitope when he proposed that an antigen particle carries several epitopes [38]. Many epitopes are antigenic determinants expressed on the molecular surface of antigen [20][21][22][23]. Others are hidden epitopes (or cryptotopes) that become immunologically available after fragmentation or denaturation of antigen.…”

Section: Structural and Functional Definition Of An Epitopementioning

confidence: 99%

“…This means that with about 15-22 contact residues, a structural epitope comprises a rather large area on the antigen surface and involves many amino acid residues that make contact with a large group of residues on CDRs collectively referred to as the paratope of antibody. Direct contact between epitope and paratope residues is established through electrostatic forces such as hydrogen bonds, salt bridges, van der Waals forces of hydrophobic surfaces and shape complementarity [20][21][22][23]. The interface has also bound water molecules or other co-factors that contribute to the specificity and affinity of antigen-antibody interactions [42].…”

Section: Structural and Functional Definition Of An Epitopementioning

confidence: 99%

“…This is not surprising because Hyb3 is specific for an HLArestricted peptide. Similar to the CDRs of TCR α and β chains [20][21][22][23], Hyb3 uses its H and L chain CDRs to form an interface with the antigenic peptide and the α helices of HLA. The interface has however a different architecture in that Hyb3 has an angled orientation and contact the C-terminus rather than the center of peptide [76].…”

Section: Structural Aspects Of Immune Complexes Involving Hla Moleculesmentioning

confidence: 99%

“…This experience suggests that the structural definition of epitopes should use expanded criteria including longer sequences and residues in discontinuous sequence positions. Such criteria should consider the structural basis of antibody-antigen interactions including contact areas and binding energy, the essence of antigenicity [20][21][22][23]. This report describes how these concepts can be applied to the HLAMatchmaker algorithm to define structural histocompatibility at the humoral immune level.…”

Section: Introductionmentioning

confidence: 99%

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

2006

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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.

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Section: Structural and Functional Definition Of An Epitopementioning

confidence: 99%

Section: Structural and Functional Definition Of An Epitopementioning

confidence: 99%

Section: Structural Aspects Of Immune Complexes Involving Hla Moleculesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

2006

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“…Comparison to Other Ig Fold-containing Proteins The regions of immunoglobulins and Ig-like T cell surface molecules implicated in both homophilic and heterophilic interactions are on the GFCC'C" face of the 13 sheet (Chothia et al, 1985;Amit et al, 1986; Vol 7, January 1996 Colman et al, 1987;Sheriff et al, 1987;Alzari et al, 1988;Clayton et al, 1988;Colman, 1988;Peterson and Seed, 1988;Arthos et al, 1989;Ashkenazi et al, 1990;Driscoll et al, 1991;Fleury et al, 1991;Jones et al, 1992;Leahy et al, 1992;Arulanandam et al, 1993). Recent results indicate that some proteins with no significant sequence similarity to the Ig superfamily have a / sheet structure that resembles the Ig fold.…”

Section: Protein Analysismentioning

confidence: 99%

Identification of a ligand-binding site in an immunoglobulin fold domain of the Saccharomyces cerevisiae adhesion protein alpha-agglutinin.

Nobel

Lipke

Kurjan

1996

MBoC

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The Saccharomyces cerevisiae adhesion protein a-agglutinin (Agalp) is expressed by a cells and binds to the complementary a-agglutinin expressed by a cells. The N-terminal half of a-agglutinin is sufficient for ligand binding and has been proposed to contain an immunoglobulin (Ig) fold domain. Based on a structural homology model for this domain and a previously identified critical residue (His292), we made Agalp mutations in three discontinuous patches of the domain that are predicted to be in close proximity to His292 in the model. Residues in each of the three patches were identified that are important for activity and therefore define a putative ligand binding site, whereas mutations in distant loops had no effect on activity. This putative binding site is on a different surface of the Ig fold than the defined binding sites of immunoglobulins and other members of the Ig superfamily. Comparison of protein interaction sites by structural and mutational analysis has indicated that the area of surface contact is larger than the functional binding site identified by mutagenesis. The putative a-agglutinin binding site is therefore likely to identify residues that contribute to the functional binding site within a larger area that contacts a-agglutinin.

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VL:VH domain rotations in engineered antibodies: Crystal structures of the Fab fragments from two murine antitumor antibodies and their engineered human constructs

et al. 1997

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The crystal structures of two pairs of Fab fragments have been determined. The pairs comprise both a murine and an engineered human form, each derived from the antitumor antibodies A5B7 and CTM01. Although antigen specificity is maintained within the pairs, antigen affinity varies. A comparison of the hypervariable loops for each pair of antibodies shows their structure has been well maintained in grafting, supporting the canonical loop model. Detailed structural analysis of the binding sites and domain arrangements for these antibodies suggests the differences in antigen affinity observed are likely to be due to inherent flexibility of the hypervariable loops and movements at the VL:VH domain interface. The four structures provide the first opportunity to study in detail the effects of protein engineering on specific antibodies.

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Structure of Antibody-Antigen Complexes: Implications for Immune Recognition

Cited by 207 publications

References 124 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

Identification of a ligand-binding site in an immunoglobulin fold domain of the Saccharomyces cerevisiae adhesion protein alpha-agglutinin.

VL:VH domain rotations in engineered antibodies: Crystal structures of the Fab fragments from two murine antitumor antibodies and their engineered human constructs

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