Predicting the immunogenicity of human leukocyte antigen class I alloantigens using structural epitope analysis determined by HLAMatchmaker.
BACKGROUND
Human leukocyte antigen (HLA) matching strategies for kidney transplantation assign equal weighting to mismatches at a particular locus and take no account of variation in immunogenicity according to recipient HLA type. We examined the ability of intra- and interlocus analysis of amino-acid polymorphisms at continuous (triplet) and discontinuous positions (eplet) defined by the HLAMatchmaker program to predict alloantigen immunogenicity.


METHODS
Sera from highly sensitized patients were screened for HLA class-I alloantibodies and mismatched combinations were analyzed using HLAMatchmaker to determine the number of triplet or extended-triplet and eplet mismatches.


RESULTS
Logistic regression analysis revealed a strong correlation between the number of triplet or extended-triplet and eplet mismatches and both the presence and magnitude of alloantibody to mismatched HLA-A and -B specificities. The additional structural information provided by eplet analysis gave increased discrimination of mismatched-HLA specificities for alloantigens with greatest sequence disparity but this did not further improve the ability of triplet analysis to predict alloantigen immunogenicity. High antibody levels were observed for several mismatched-HLA combinations with zero triplet or eplet mismatches indicating that self triplets or eplets expressed in different conformations do not always predict nonimmunogenic epitopes.


CONCLUSIONS
Analysis of recipient HLA type and mismatched-HLA alloantigens using the HLAMatchmaker algorithm allows prediction of immunogenic donor HLA types.
Kosmoliaptsis
Vasilis
V
Tissue Typing Laboratory, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge, United Kingdom.
Bradley
J Andrew
JA
Sharples
Linda D
LD
Chaudhry
Afzal
A
Key
Timothy
T
Goodman
Reyna S
RS
Taylor
Craig J
CJ
D000328:Adult; D000465:Algorithms; D000596:Amino Acids / Q000276:immunology; D000906:Antibodies / Q000276:immunology; D000939:Epitopes / Q000235:genetics* / Q000276:immunology; D005260:Female; D005805:Genes, MHC Class I / Q000235:genetics* / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D006801:Humans; D007125:Immunogenetics; D007519:Isoantigens / Q000235:genetics* / Q000276:immunology; D016030:Kidney Transplantation / Q000276:immunology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests
D000596:Amino Acids; D000906:Antibodies; D000939:Epitopes; D007519:Isoantigens