HLAMatchmaker-Based Analysis of Human Monoclonal Antibody Reactivity Demonstrates the Importance of an Additional Contact Site for Specific Recognition of Triplet-Defined Epitopes

Duquesnoy, René J.; Mulder, Arend; Askar, Medhat; Fernández-Viña, Marcelo; Claas, Frans H.J.

doi:10.1016/j.humimm.2005.04.002

Cited by 58 publications

(57 citation statements)

References 40 publications

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“…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: Discussionmentioning

confidence: 67%

“…This algorithm has been verified by observations that many serologically defined private and public epitopes correspond to triplets and that an HLAMatchmaker-based analysis of serum reactivity is useful in predicting of cross-match results with potential donors [8,10,12,13,16]. Recent studies on human anti-HLA monoclonal antibodies have however, indicated that HLA epitopes include additional polymorphic residues located nearby triplets on the molecular surface [19]. Moreover, certain serologically defined antigenic determinants do not have corresponding triplets.…”

Section: Introductionmentioning

confidence: 91%

“…Our recent study on triplet-specific human monoclonal antibodies has shown that antibody binding depends on the presence of one or more additional residues shared between the immunizing antigen and the triplet-carrying reactive alleles [19]. For instance, the reactivity of an anti-62QE monoclonal antibody (mAb) requires the presence of a glycine residue in position 56.…”

Section: Two-patch Shape Of Hla Epitopesmentioning

confidence: 99%

“…The first is a group of antigens in the A1 CREG that share four patches. We have recently described a human monoclonal antibody reacting with this antigen group [19]. The second is a well-known group of B7-CREG antigens that has the same six overlapping patches.…”

Section: Construction Of a Structural Model For Functional Epitopes Omentioning

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: Discussionmentioning

confidence: 67%

Section: Introductionmentioning

confidence: 91%

Section: Two-patch Shape Of Hla Epitopesmentioning

confidence: 99%

Section: Construction Of a Structural Model For Functional Epitopes Omentioning

confidence: 99%

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

2006

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“…11 Antikora erişebilecek pozisyonda olan aminoasitler, proteinin alfa-heliks (Şekil 1'de sarmal şeklinde görülen kısım) ve beta loop (Şekil 1'de köprü şeklinde olan kısım örneğin; 12S-20F bölgesi) kısımlarındadır. 13,14 HLA "matchmaker" programı, tmm (uyumsuz) sürümü ile Sınıf I antijeninin antikor ile etkileşen rezidülerin (kalıntı, belirli pozisyonlardaki aminoasitleri ifade etmektedir) üçlü aminaosit dizisini esas almaktadır. Hasta ve donörün tripletlerini karşılaştırarak alıcı-donör çifti arasında kaç tmm olduğunu saptamaktadır.…”

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Investigation of Human Leucocyte Antigen Epitopes in Organ Transplantation: Review

Ayna¹,

Pirim²

2017

Turkiye Klinikleri J Intern Med

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Transplantation Genetics

Graziano¹,

Trucco²

2019

Emery and Rimoin's Principles and Practice of Medical Genetics and Genomics

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HLAMatchmaker-Based Analysis of Human Monoclonal Antibody Reactivity Demonstrates the Importance of an Additional Contact Site for Specific Recognition of Triplet-Defined Epitopes

Cited by 58 publications

References 40 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

Investigation of Human Leucocyte Antigen Epitopes in Organ Transplantation: Review

Transplantation Genetics

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