Human leukocyte antigen class II DQ alpha and beta epitopes identified from sera of kidney allograft recipients.
BACKGROUND
Epitopes are the sites to which antibodies bind. Both alpha and beta peptide chains of the human leukocyte antigen-DQ heterodimers (DQA1 and DQB1, respectively) contain polymorphic regions. We can identify DQA1 and DQB1 epitopes by DQ single antigen beads assay of the antibodies, correlating the beads' reaction patterns with either DQA1 or DQB1 alleles.


METHODS
Sera from 74 transplant patients and 35 mouse DQB1 monoclonal antibodies were tested with DQ single antigen beads for their DQ allelic and serological specificities. Epitopes were defined by amino acids shared by the positive antigens of the antibodies. Unique amino acids were identified as potential epitope sites by comparing the peptide sequences of all human leukocyte antigen class II alleles. For the absorption or elution, patient's serum sample was absorbed by a homozygous B-lymphoblast cell line of specific DQ typing, the eluted antibody then tested with single antigen beads to demonstrate that the antibody reacted to a single epitope shared by multiple DQ antigens.


RESULTS
Three DQA1 and 15 DQB1 epitopes were identified. We found that 21 patients produced antibodies against one of the DQA1 epitopes; 27 patients produced antibodies against one of the DQB1 epitopes.


CONCLUSIONS
The DQA1 and DQB1 epitopes identified here seem to be immunogenic and to elicit DQ antibodies. For the DQB1 epitopes, multiple DQ serological specificities that were detected in the serum of a transplant patient could be explained as a single donor-specific DQ antibody reacting to a mismatched DQ epitope of the donor. Ten examples are shown here.
Deng
Chun-Tsan
CT
One Lambda Inc., Canoga Park, CA, USA. cdeng@terasakilab.org
El-Awar
Nadim
N
Ozawa
Miyuki
M
Cai
Junchao
J
Lachmann
Nils
N
Terasaki
Paul I
PI
D000818:Animals; D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D001402:B-Lymphocytes / Q000276:immunology; D002460:Cell Line; D018604:Epitope Mapping; D006084:Graft Rejection / Q000276:immunology*; D006683:HLA-DQ Antigens / Q000276:immunology*; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; D006650:Histocompatibility Testing; D006801:Humans; D007163:Immunosorbent Techniques; D007518:Isoantibodies / Q000097:blood*; D016030:Kidney Transplantation; D051379:Mice; D013997:Time Factors; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen; D007518:Isoantibodies