Human leukocyte antigen epitope antigenicity and immunogenicity

Duquesnoy, René J.

doi:10.1097/mot.0000000000000100

Cited by 53 publications

(43 citation statements)

References 29 publications

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“…Studies to identify HLA epitope, the target of antibodies, started more than 50 years ago [10], and numerous other studies followed since then [5, 6, 11, 28–34]. The amino acid structure of HLA antigen chains was reported for the HLA A2 in 1987 [12], and now, complete sequences of all known HLA antigen chains are readily available online [23].…”

Section: Discussionmentioning

confidence: 99%

HLA Epitopes: The Targets of Monoclonal and Alloantibodies Defined

El‐Awar

Jucaud

Nguyen

2017

Journal of Immunology Research

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Sensitization to human leukocyte antigens (HLA) in organ transplant patients causes graft rejection, according to the humoral theory of transplantation. Sensitization is almost ubiquitous as anti-HLA antibodies are found in almost all sera of transplant recipients. Advances in testing assays and amino acid sequencing of HLA along with computer software contributed further to the understanding of antibody-antigen reactivity. It is commonly understood that antibodies bind to HLA antigens. With current knowledge of epitopes, it is more accurate to describe that antibodies bind to their target epitopes on the surface of HLA molecular chains. Epitopes are present on a single HLA (private epitope) or shared by multiple antigens (public epitope). The phenomenon of cross-reactivity in HLA testing, often explained as cross-reactive groups (CREGs) of antigens with antibody, can be clearly explained now by public epitopes. Since 2006, we defined and reported 194 HLA class I unique epitopes, including 56 cryptic epitopes on dissociated HLA class I heavy chains, 83 HLA class II epitopes, 60 epitopes on HLA-DRB1, 15 epitopes on HLA-DQB1, 3 epitopes on HLA-DQA1, 5 epitopes on HLA-DPB1, and 7 MICA epitopes. In this paper, we provide a summary of our findings.

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Section: Discussionmentioning

confidence: 99%

HLA Epitopes: The Targets of Monoclonal and Alloantibodies Defined

El‐Awar

Jucaud

Nguyen

2017

Journal of Immunology Research

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“…16-19 Although increasing number of eplet HLA mismatches may increase the chance of developing dn DSA and acute rejection, the immunogenic potential of eplet mismatches may be dependent on the nature and binding capacity of each eplet HLA mismatch. 20,21 …”

Section: Discussionmentioning

confidence: 99%

The Association Between Broad Antigen HLA Mismatches, Eplet HLA Mismatches and Acute Rejection After Kidney Transplantation

Nguyen

Wong

Chapman

et al. 2016

Transplantation Direct

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“…24,25 In particular, every individual has a repertoire of B cells with low avidity for epitopes of receptors expressed on own cells that does not lead to the activation of B cells and antibody production, although exposure to non-self epitopes can induce an antibody response. 26 Thus, an auto reactive component is also required for alloantibody responses to an HLA mismatch. 27 In the present study, in accordance with Lopes and associates, 7 we confirmed that a transplant has a high immunizing effect for both HLA class I and II compared with pregnancy and transfusion.…”

Section: Discussionmentioning

confidence: 99%

Untitled

Resse¹,

Paolillo²,

Minucci³

et al. 2018

Exp Clin Transplant

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Objectives: Human leukocyte antigen alloimmunization is caused by exposure to HLA antigens through transfusion, pregnancy, or transplant. Our study objective was to present the rate of positivity of anti-HLA antibody considering the effects of a single sensitization event in kidney transplant candidates at our center. Materials and Methods: Our study reviewed 606 kidney transplant candidates. Patient sera were analyzed using Luminex xMAP technology. Panel reactive antibody positivity rates and antibody strengths in patients were analyzed according to a single sensitization event. Results: Our findings showed 246 patients (40.6%) with a panel reactive antibody > 0, of which 97 (39.4%) were sensitized from a single event, 119 (48.4%) were sensitized by multiple events, and 30 (12.2%) had no known sensitizing event. Considering patients sensitized by a single event with a panel reactive antibody > 0, we found that 25.8% had received transplant only, 49.5% had previous pregnancy only, and 24.7% had received transfusion only. The strength of antibodies was significantly higher in patients with previous transplant procedures than in those with transfusion for HLA-A (P < .01), HLA-B (P < .05), HLA-C (P < .05), HLA-DR (P < .001), HLA-DQ (P < .05), and HLA-DP (P < .05). Similarly, we observed significantly higher median fluorescence intensity values for HLA-A, -DR, -DQ, and -DP loci in patients with a previous transplant procedure versus preg nancy. The strength of antibodies against HLA-DR was significantly higher in patients with a previous pregnancy compared with those with transfusion (P < .01). Conclusions: This study documents the profile of HLA alloimmunization in kidney transplant candidates. In particular, transplant procedures appear to have a greater immunologic impact, followed by pregnancy and transfusion. Our data confirm and are in accordance with those of several studies in which the sensitization events were associated with higher prevalence of anti-HLA antibodies.

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Human leukocyte antigen epitope antigenicity and immunogenicity

Abstract: These findings support the usefulness of HLA matching at the epitope level, including the identification of acceptable mismatches for sensitized patients and permissible mismatching for nonsensitized patients aimed to reduce HLA antibody responses.

Cited by 53 publications

References 29 publications

HLA Epitopes: The Targets of Monoclonal and Alloantibodies Defined

HLA Epitopes: The Targets of Monoclonal and Alloantibodies Defined

The Association Between Broad Antigen HLA Mismatches, Eplet HLA Mismatches and Acute Rejection After Kidney Transplantation

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