Epitopes of HLA Antibodies Found in Sera of Normal Healthy Males and Cord Blood.

El-Awar N, Terasaki PI, Nguyen A, Sasaki N, Morales-Buenrostro LE, Saji H, Maruya E, Poli F.

Clinical Transplants 2008, Chapter 19

Abstract

This chapter defines epitopes targeted by antibodies in the sera of two populations of healthy normal males and in cord blood samples from a third population. These epitopes are accessible for antibody binding on either the intact or dissociated forms of recombinant HLA class I single antigens. Sixty percent of these epitopes are defined by hidden amino acids, and are therefore designated as cryptic epitopes. All sera were tested in parallel, using single antigen beads that bore either intact or dissociated recombinant HLA antigens. Ninety-six HLA class I epitopes were characterized as epitopes of these antibodies. More than half were private epitopes, and the rest were shared by two-to-18 HLA antigens. Fifty-eight (60%) epitopes were accessible on dissociated HLA antigens. Of these, 41 were defined by hidden amino acids, 13 by at least one hidden amino acid in addition to exposed amino acids, and four were defined by exposed amino acids. Almost all epitopes were found exclusively on either A-, B-, or C-locus antigens--except for one inter-locus epitope. Antibodies with nearly identical specificities were found in all three of the tested populations. Most of these antibodies target epitopes that are accessible only on the dissociated forms of the HLA class I antigens. Specificities of such antibodies are unavoidably detected when testing for specificities of alloantibodies so it may be necessary to clearly differentiate the two forms of antibody. The relevance of these antibodies in transplantation is not yet known. But even if they are shown to be irrelevant to graft rejection, awareness of the newly identified epitopes could prove useful in avoiding unnecessary exclusion of potential transplant donors.